Key associations for hepatitis C virus genotypes in the Middle East and North Africa.

This study aimed to investigate the epidemiology of hepatitis C virus (HCV) genotypes in the Middle East and North Africa (MENA) through an analytical and quantitative meta-regression methodology. For the most common genotypes 1, 3, and 4, country/subregion explained more than 77% of the variation in the distribution of each genotype. Genotype 1 was common across MENA, and was more present in high-risk clinical populations than in the general population. Genotype 3 was much more present in Afghanistan, Iran, and Pakistan than the rest of countries, and was associated with transmission through injecting drug use. Genotype 4 was broadly disseminated in Egypt in all populations, with overall limited presence elsewhere. While genotype 2 was more present in high-risk clinical populations and people who inject drugs, most of the variation in its distribution remained unexplained. Genotypes 5, 6, and 7 had low or no presence in MENA, limiting the epidemiological inferences that could be drawn. To sum up, geography is the principal determinant of HCV genotype distribution. Genotype 1 is associated with transmission through high-risk clinical procedures, while genotype 3 is associated with injecting drug use. These findings demonstrate the power of such analytical approach, which if extended to other regions and globally, can yield relevant epidemiological inferences.

Hepatitis C virus genotypes in the Middle East and North Africa: Distribution, diversity, and patterns.

Our objective was to characterize the distribution, diversity and patterns of hepatitis C virus (HCV) genotypes in the Middle East and North Africa (MENA). Source of data was a database of HCV genotype studies in MENA populated using a series of systematic literature searches. Pooled mean proportions were estimated for each genotype and by country using DerSimonian-Laird random-effects meta-analyses. Genotype diversity within countries was assessed using Shannon Diversity Index. Number of chronic infections by genotype and country was calculated using the pooled proportions and country-specific numbers of chronic infection. Analyses were conducted on 338 genotype studies including 82 257 genotyped individuals. Genotype 1 was dominant (≥50%) in Algeria, Iran, Morocco, Oman, Tunisia, and UAE, and was overall ubiquitous across the region. Genotype 2 was common (10-50%) in Algeria, Bahrain, Libya, and Morocco. Genotype 3 was dominant in Afghanistan and Pakistan. Genotype 4 was dominant in Egypt, Iraq, Jordan, Palestine, Qatar, Saudi Arabia, and Syria. Genotypes 5, 6, and 7 had limited or no presence across countries. Genotype diversity varied immensely throughout MENA. Weighted by population size, MENA's chronic infections were highest among genotype 3, followed by genotype 4, genotype 1, genotype 2, genotype 5, and genotype 6. Despite ubiquitous presence of genotype 1, the vast majority of chronic infections were of genotypes 3 or 4, because of the sizable epidemics in Pakistan and Egypt. Three sub-regional patterns were identified: genotype 3 pattern centered in Pakistan, genotype 4 pattern centered in Egypt, and genotype 1 pattern ubiquitous in most MENA countries.

Characterising the progress in HIV/AIDS research in the Middle East and North Africa.

OBJECTIVES: The Middle East and North Africa (MENA) region is perceived to have limited HIV data. The objective of this study was to quantitatively characterise the progress in HIV research in this region since the discovery of the epidemic. METHODS: Four indices were defined and implemented to measure the progress of HIV research using the PubMed, Embase, MENA HIV/AIDS Epidemiology Synthesis Project and US Census Bureau HIV/AIDS Surveillance databases. The four indices provide complementary measures to characterise different aspects of the progress of HIV research. RESULTS: A total of 2118, 2352, 683 and 4889 records were identified through the PubMed, the Embase, the Synthesis Project and the HIV Prevalence indices, respectively. The proportion of the total global HIV records that relate to MENA is 1.2%. Overall, the indices show steady progress in the number of new records every year, with an accelerated pace in the last few years. The rate of progress in MENA was also higher than the rate of progress in HIV records globally. There is no evidence so far of stabilisation or a peak in the number of new records year by year. About half of the records were produced after the year 2005. The number of records shows large heterogeneity across countries. CONCLUSIONS: MENA has witnessed a rapid growth in HIV research over the last decade. However, there are still large gaps in HIV scientific evidence in the region, and the progress is far from being uniform across countries. Ongoing and future research needs to be geared towards academic standard and production of scientific publications.

The distribution of new HIV infections by mode of exposure in Morocco.

OBJECTIVES: Building on a wealth of new empirical data, the objective of this study was to estimate the distribution of new HIV infections in Morocco by mode of exposure using the modes of transmission (MoT) mathematical model. METHODS: The MoT model was implemented within a collaboration with the Morocco Ministry of Health and the Joint United Nations Programme on HIV/AIDS. The model was parameterised through a comprehensive review and synthesis of HIV and risk behaviour data in Morocco, mainly through the Middle East and North Africa HIV/AIDS Synthesis Project. Uncertainty analyses were used to assess the reliability of and uncertainty around our calculated estimates. RESULTS: Female sex workers (FSWs), clients of FSWs, men who have sex with men (MSM) and injecting drug users (IDUs) contributed 14%, 24%, 14% and 7% of new HIV infections, respectively. Two-thirds (67%) of new HIV infections occurred among FSWs, clients of FSWs, MSM and IDUs, or among the stable sexual partners of these populations. Casual heterosexual sex contributed 7% of HIV infections. More than half (52%) of HIV incidence is among females, but 71% of these infections are due to an infected spouse. The vast majority of HIV infections among men (89%) are due to high-risk behaviour. A very small HIV incidence is predicted to arise from medical injections or blood transfusions (0.1%). CONCLUSIONS: The HIV epidemic in Morocco is driven by HIV incidence in high-risk population groups, with commercial heterosexual sex being the largest contributor to incidence. There is a need to focus HIV response more on these populations, mainly through proactive and sustainable HIV surveillance, and the expansion and increased geographical coverage of services such as condom promotion among FSWs, voluntary counselling and testing, harm reduction and treatment.

Characterizing the historical role of parenteral antischistosomal therapy in hepatitis C virus transmission in Egypt.

BACKGROUND: Egypt is the nation most affected by hepatitis C virus (HCV) infection, following an epidemic of historic proportions. We aimed to characterize the epidemic's historical evolution and to delineate the role of parenteral antischistosomal therapy (PAT) campaigns in transmission. METHODS: A mathematical model was constructed and analysed in order to understand HCV-transmission dynamics. The model was fitted to Egypt's Demographic and Health Survey data and to a systematic database of HCV-prevalence data. RESULTS: The incidence rate peaked in 1966 at 15.7 infections per 1000 person-years-a period of time that coincides with the PAT campaigns-and rapidly declined thereafter, beginning the mid-1990s. The annual number of new infections peaked in 1993 at 581 200 (with rapid demographic growth), leading to a high-incidence-cohort effect, and declined to 67 800 by 2018. The number of individuals ever infected (1950-2018) was 16.4 million, with HCV prevalence peaking in 1979. The number of individuals ever exposed to PAT was 8.3 million; however, of these individuals, 7.3 million were alive in 1980 and only 3.5 million alive in 2018. The number of individuals ever infected due to PAT exposure was 963 900, with 850 200 individuals alive in 1980 and only 389 800 alive in 2018. The proportion of PAT-attributed prevalent infections peaked at 19.9% in 1972, declining to 5.5% by 2018. CONCLUSIONS: PAT campaigns played an important role in HCV transmission, yet explain only 6% of infections-they appear to be a manifestation, rather than a cause, of the epidemic. A possible driver of the epidemic could be the mass expansion of inadequate-quality healthcare during PAT campaigns and subsequent decades. Despite a historic toll, the epidemic has been rapidly diminishing since the mid-1990s.

Hepatitis C Virus Infection in Populations With Liver-Related Diseases in the Middle East and North Africa.

We investigated hepatitis C virus (HCV) epidemiology in populations with liver-related diseases (LRDs) in the Middle East and North Africa. The data source was standardized databases of HCV measures populated through systematic reviews. Random-effects meta-analyses and meta-regressions were performed, and genotype diversity was assessed. Analyses were based on 252 HCV antibody prevalence measures, eight viremic rate measures, and 30 genotype measures on 132,358 subjects. Pooled mean prevalence in LRD populations was 58.8% (95% confidence interval [CI], 51.5%-66.0%) in Egypt and 55.8% (95% CI, 49.1%-62.4%) in Pakistan; these values were higher than in other countries, which had a pooled prevalence of only 15.6% (95% CI, 12.4%-19.0%). Mean prevalence was highest in patients with hepatocellular carcinoma at 56.9% (95% CI, 50.2%-63.5%) and those with cirrhosis at 50.4% (95% CI, 40.8%-60.0%). Type of LRD population and country were the strongest predictors of prevalence, explaining 48.6% of the variation. No evidence for prevalence decline was found, but there was strong evidence for prevalence increase in Pakistan. A strong, positive association was identified between prevalence in the general population and that in LRD populations; the Pearson correlation coefficient ranged between 0.605 and 0.862. The pooled mean viremic rate was 75.5% (95% CI, 61.0%-87.6%). Genotype 4 was most common (44.2%), followed by genotype 3 (34.5%), genotype 1 (17.0%), genotype 2 (3.5%), genotype 6 (0.5%), and genotype 5 (0.3%). Conclusion: HCV appears to play a dominant role in liver diseases in Egypt and Pakistan and has a growing role in Pakistan. Testing and treatment of LRD populations are essential to reduce disease burden and transmission and to reach HCV elimination by 2030.

The status of hepatitis C virus infection among people who inject drugs in the Middle East and North Africa.

BACKGROUND AND AIMS: People who inject drugs (PWID) are a key population at high risk of hepatitis C virus (HCV) infection. The aim of this study was to delineate the epidemiology of HCV in PWID in the Middle East and North Africa (MENA). METHODS: Syntheses of data were conducted on the standardized and systematically assembled databases of the MENA HCV Epidemiology Synthesis Project, 1989-2018. Random-effects meta-analyses and meta-regressions were performed. Meta-regression variables included country, study site, year of data collection and year of publication [to assess trends in HCV antibody prevalence over time], sample size and sampling methodology. Numbers of chronically infected PWID across MENA were estimated. The Shannon Diversity Index was calculated to assess genotype diversity. RESULTS: Based on 118 HCV antibody prevalence measures, the pooled mean prevalence in PWID for all MENA was 49.3% [95% confidence interval (CI) = 44.4-54.1%]. The country-specific pooled mean ranged from 21.7% (95% CI = 4.9-38.6%) in Tunisia to 94.2% (95% CI = 90.8-96.7%) in Libya. An estimated 221 704 PWID were chronically infected, with the largest numbers found in Iran at 68 526 and in Pakistan at 46 554. There was no statistically significant evidence for a decline in HCV antibody prevalence over time. Genotype diversity was moderate (Shannon Diversity Index of 1.01 out of 1.95; 52.1%). The pooled mean percentage for each HCV genotype was highest in genotype 3 (42.7%) and in genotype 1 (35.9%). CONCLUSION: Half of people who inject drugs in the Middle East and North Africa appear to have ever been infected with hepatitis C virus, but there are large variations in antibody prevalence among countries. In addition to > 200 000 chronically infected current people who inject drugs, there is an unknown number of people who no longer inject drugs who may have acquired hepatitis C virus during past injecting drug use. Harm reduction services must be expanded, and innovative strategies need to be employed to ensure accessibility to hepatitis C virus testing and treatment.

Who to Test for Hepatitis C Virus in the Middle East and North Africa?: Pooled Analyses of 2,500 Prevalence Measures, Including 49 Million Tests.

Expanding hepatitis C virus (HCV) treatment coverage is challenged by limited testing and diagnosis. This study assessed the risk of exposure, for the Middle East and North Africa, by population, yields of testing, and program efficiency of testing strategies. A standardized and systematically assembled database of 2,542 HCV antibody prevalence studies on 49 million individuals was analyzed. Random effects meta-analyses were conducted to estimate pooled measures for risk of exposure, risk ratio (RR) of exposure, and yields of testing. Program expansion path curves were calculated to assess program efficiency. Countries clustered into two patterns: generalized versus concentrated epidemics. In generalized epidemics (Egypt and Pakistan) relative to general populations, RR of exposure was 6.8 for people who inject drugs (PWID), 6.7 for populations with liver conditions, and 5.0 for populations with high-risk health care exposures. In concentrated epidemics (remaining countries), corresponding RRs were 97.2, 45.1, and 22.2, respectively. In generalized epidemics, the number of tests needed to identify a chronic infection was 2.5 for PWID, 2.4 for populations with liver conditions, 2.7 for populations with high-risk health care exposures, and 14.2 for general populations. In concentrated epidemics, corresponding numbers were 2.8, 8.6, 5.1, and 222.2, respectively. Program expansion path curves demonstrated major gains in program efficiency by targeting specific populations. Risk of exposure varies immensely by population and shows a distinctive hierarchy, particularly in concentrated epidemics. Testing strategies can be much more efficient through population prioritization by risk of exposure. General population testing is not programmatically efficient in concentrated epidemics.

Characterizing hepatitis C virus epidemiology in Egypt: systematic reviews, meta-analyses, and meta-regressions.

Egypt is the most affected nation by hepatitis C virus (HCV) and needs a comprehensive characterization of HCV epidemiology to inform the scale-up of treatment and prevention programs. Systematic reviews, meta-analyses, and meta-regressions were conducted. A total of 25 incidence, 259 prevalence, and 47 genotype studies were identified. Incidence and prevalence levels were high across all populations. Genotype 4 accounted for 94.1% of infections with a relative Shannon Diversity Index of only 14.4%. Pooled mean HCV prevalence was estimated at 11.9% (95% CI = 11.1-12.6%) among the general population, 55.6% (95% CI = 49.4-61.7%) among populations at high risk, 14.3% (95% CI = 10.3-18.8%) among populations at intermediate risk, 56.0% (95% CI = 50.4-61.6%) among populations with liver-related conditions, and 35.0% (95% CI = 27.3-43.1%) among special clinical populations. Mean HCV viremic rate was estimated at 66.7% (95% CI = 61.7-71.5%). Meta-regression indicated 6% lower odds for HCV prevalence for each one-year increment in publication year (AOR = 0.94; 95% CI = 0.92-0.96). HCV prevalence is high with evidence for ongoing transmission mainly through healthcare. Genotype diversity is low with genotype 4 dominance. Two-thirds of antibody-positive Egyptians are chronically infected and need treatment. Clinical populations should be prioritized for screening. Despite the large-scale epidemic, prevalence appears to be declining rapidly consistent with a contracting epidemic.

The epidemiology of hepatitis C virus in Pakistan: systematic review and meta-analyses.

To characterize hepatitis C virus (HCV) epidemiology in Pakistan and estimate the pooled mean HCV antibody prevalence in different risk populations, we systematically reviewed all available records of HCV incidence and/or prevalence from 1989 to 2016, as informed by the Cochrane Collaboration Handbook. This systematic review was reported following the PRISMA guidelines. Populations were classified into six categories based on the risk of exposure to HCV infection. Meta-analyses were performed using DerSimonian and Laird random-effects models with inverse variance weighting. The search identified one HCV incidence study and 341 prevalence measures/strata. Meta-analyses estimated the pooled mean HCV prevalence at 6.2% among the general population, 34.5% among high-risk clinical populations, 12.8% among populations at intermediate risk, 16.9% among special clinical populations, 55.9% among populations with liver-related conditions and 53.6% among people who inject drugs. Most reported risk factors in analytical epidemiologic studies related to healthcare procedures. Pakistan is enduring an HCV epidemic of historical proportions-one in every 20 Pakistanis is infected. HCV plays a major role in liver disease burden in this country, and HCV prevalence is high in all-risk populations. Most transmission appears to be driven by healthcare procedures. HCV treatment and prevention must become a national priority.

Individual-level key associations and modes of exposure for hepatitis C virus infection in the Middle East and North Africa: a systematic synthesis.

PURPOSE: To identify, map, and synthesize the individual-level key associations and modes of exposure for hepatitis C virus (HCV) infection in the Middle East and North Africa (MENA), the most affected region by HCV. METHODS: Source of data was the MENA HCV Epidemiology Synthesis Project database, populated through systematic literature searches. Risk factors determined to be statistically significant after adjustment for confounders were extracted and categorized into key associations or modes of exposure. RESULTS: In total, 329 risk factors were identified from 109 articles in 14 of 24 MENA countries. Among key associations, age was most frequently reported (n = 39; 34.2%), followed by other infections/diseases (n = 20; 17.5%), and incarceration (n = 17; 14.9%). Among modes of exposure, health care-related exposures were most frequently reported (n = 127; 59.5%), followed by injecting drug use exposures (n = 45; 20.9%), community-related exposures (n = 34; 15.8%), and sexual-related exposures (n = 8; 3.7%). Blood transfusion, hemodialysis, surgical and other medical procedures, dental work, and medical injections were identified as key health care-related exposures. CONCLUSIONS: Health care appears to be the primary driver of prevalent (and possibly incident) infections in MENA, followed by injecting drug use. HCV screening should target the identified modes of exposure. Commitment to prevention should be an integral component of HCV response to achieve HCV elimination by 2030, with focus on strengthening infection control in health care facilities, improving injection safety and blood screening, and expanding harm reduction services for people who inject drugs.

Global population-level association between herpes simplex virus 2 prevalence and HIV prevalence.

BACKGROUND: Our objective was to assess the population-level association between herpes simplex virus 2 (HSV-2) and HIV prevalence. METHODS: Reports of HSV-2 and HIV prevalence were systematically reviewed and synthesized following PRISMA guidelines. Spearman rank correlation ((Equation is included in full-text article.)) was used to assess correlations. Risk ratios (RRHSV-2/HIV) and odds ratios (ORHSV-2/HIV) were used to assess HSV-2/HIV epidemiologic overlap. DerSimonian-Laird random-effects meta-analyses were conducted. RESULTS: In total, 939 matched HSV-2/HIV prevalence measures were identified from 77 countries. HSV-2 prevalence was consistently higher than HIV prevalence. Strong HSV-2/HIV prevalence association was found for all data ((Equation is included in full-text article.) = 0.6, P < 0.001), all data excluding people who inject drugs (PWID) and children ((Equation is included in full-text article.) = 0.7, P < 0.001), female sex workers ((Equation is included in full-text article.) = 0.5, P < 0.001), and MSM ((Equation is included in full-text article.) = 0.7, P < 0.001). No association was found for PWID ((Equation is included in full-text article.) = 0.2, P = 0.222) and children ((Equation is included in full-text article.) = 0.3, P = 0.082). A threshold effect was apparent where HIV prevalence was limited at HSV-2 prevalence less than 20%, but grew steadily with HSV-2 prevalence for HSV-2 prevalence greater than 20%. The overall pooled mean RRHSV-2/HIV was 5.0 (95% CI 4.7-5.3) and ORHSV-2/HIV was 9.0 (95% CI 8.4-9.7). The RRHSV-2/HIV and ORHSV-2/HIV showed similar patterns that conveyed inferences about HSV-2 and HIV epidemiology. CONCLUSION: HSV-2 and HIV prevalence are strongly associated. HSV-2 prevalence can be used as a proxy 'biomarker' of HIV epidemic potential, acting as a 'temperature scale' of the intensity of sexual risk behavior that drive HIV transmission. HSV-2 prevalence can be used to identify populations and/or sexual networks at high-risk of future HIV expansion, and help prioritization, optimization, and resource allocation of cost-effective prevention interventions.

Mapping of new HIV infections in Morocco and impact of select interventions.

OBJECTIVES: The aim of this study was to assess HIV modes of exposure in Morocco at the national level and also for Souss-Massa-Drâa, the region most affected by HIV. Another aim was to assess the impact of different scenarios of select intervention packages. METHODS: The Modes of Transmission Model was adapted and used, and was parameterized using quality bio-behavioral surveillance data among key populations, routine data sources, and literature reviews. RESULTS: Nationally in 2013, the largest number of new infections occurred among clients of female sex workers (FSWs) (25%; 95% confidence interval (CI) 14-37%), followed by men who have sex with men (MSM) (22%; 95% CI 12-35%), HIV serodiscordant couples (22%; 95% CI 12-34%), FSWs (11%; 95% CI 6-18%), and people who inject drugs (5%; 95% CI 2-9%). A similar pattern of results was observed in Souss-Massa-Drâa, but the HIV incidence rate was four-fold that at the national level. Different scenarios of feasible intervention packages reduced HIV incidence by 8-44%. CONCLUSIONS: Commercial heterosexual sex networks continue as the leading driver of the epidemic, with half of HIV incidence. A quarter of new infections occurred among MSM, a third of which in Souss-Massa-Drâa. Feasible expanded coverage of interventions could lead to large reductions in incidence.

Hepatitis C virus viremic rate in the Middle East and North Africa: Systematic synthesis, meta-analyses, and meta-regressions.

OBJECTIVES: To estimate hepatitis C virus (HCV) viremic rate, defined as the proportion of HCV chronically infected individuals out of all ever infected individuals, in the Middle East and North Africa (MENA). METHODS: Sources of data were systematically-gathered and standardized databases of the MENA HCV Epidemiology Synthesis Project. Meta-analyses were conducted using DerSimonian-Laird random-effects models to determine pooled HCV viremic rate by risk population or subpopulation, country/subregion, sex, and study sampling method. Random-effects meta-regressions were conducted to identify predictors of higher viremic rate. RESULTS: Analyses were conducted on 178 measures for HCV viremic rate among 19,593 HCV antibody positive individuals. In the MENA region, the overall pooled mean viremic rate was 67.6% (95% CI: 64.9-70.3%). Across risk populations, the pooled mean rate ranged between 57.4% (95% CI: 49.4-65.2%) in people who inject drugs, and 75.5% (95% CI: 61.0-87.6%) in populations with liver-related conditions. Across countries/subregions, the pooled mean rate ranged between 62.1% (95% CI: 50.0-72.7%) and 70.4% (95% CI: 65.5-75.1%). Similar pooled estimates were further observed by risk subpopulation, sex, and sampling method. None of the hypothesized population-level predictors of higher viremic rate were statistically significant. CONCLUSIONS: Two-thirds of HCV antibody positive individuals in MENA are chronically infected. Though there is extensive variation in study-specific measures of HCV viremic rate, pooled mean estimates are similar regardless of risk population or subpopulation, country/subregion, HCV antibody prevalence in the background population, or sex. HCV viremic rate is a useful indicator to track the progress in (and coverage of) HCV treatment programs towards the set target of HCV elimination by 2030.

Hepatitis C Virus Epidemiology in Djibouti, Somalia, Sudan, and Yemen: Systematic Review and Meta-Analysis.

OBJECTIVES: To characterize hepatitis C virus (HCV) epidemiology and assess country-specific population-level HCV prevalence in four countries in the Middle East and North Africa (MENA) region: Djibouti, Somalia, Sudan, and Yemen. METHODS: Reports of HCV prevalence were systematically reviewed as per PRISMA guidelines. Pooled HCV prevalence estimates in different risk populations were conducted when the number of measures per risk category was at least five. RESULTS: We identified 101 prevalence estimates. Pooled HCV antibody prevalence in the general population in Somalia, Sudan and Yemen was 0.9% (95% confidence interval [95%CI]: 0.3%-1.9%), 1.0% (95%CI: 0.3%-1.9%) and 1.9% (95%CI: 1.4%-2.6%), respectively. The only general population study from Djibouti reported a prevalence of 0.3% (CI: 0.2%-0.4%) in blood donors. In high-risk populations (e.g., haemodialysis and haemophilia patients), pooled HCV prevalence was 17.3% (95%CI: 8.6%-28.2%) in Sudan. In Yemen, three studies of haemodialysis patients reported HCV prevalence between 40.0%-62.7%. In intermediate-risk populations (e.g.. healthcare workers, in patients and men who have sex with men), pooled HCV prevalence was 1.7% (95%CI: 0.0%-4.9%) in Somalia and 0.6% (95%CI: 0.4%-0.8%) in Sudan. CONCLUSION: National HCV prevalence in Yemen appears to be higher than in Djibouti, Somalia, and Sudan as well as most other MENA countries; but otherwise prevalence levels in this subregion are comparable to global levels. The high HCV prevalence in patients who have undergone clinical care appears to reflect ongoing transmission in clinical settings. HCV prevalence in people who inject drugs remains unknown.