Laith J. Abu-Raddad

Epidemiological determinants of spread of causal agent of severe acute respiratory syndrome in Hong Kong

Summary Background Health authorities worldwide, especially in the Asia Pacific region, are seeking effective public-health interventions in the continuing epidemic of severe acute respiratory syndrome (SARS). We assessed the epidemiology of SARS in Hong Kong. Methods We included 1425 cases reported up to April 28, 2003. An integrated database was constructed from several sources containing information on epidemiological, demographic, and clinical variables. We estimated the key epidemiological distributions: infection to onset, onset to admission, admission to death, and admission to discharge. We measured associations between the estimated case fatality rate and patients’age and the time from onset to admission. Findings After the initial phase of exponential growth, the rate of confirmed cases fell to less than 20 per day by April 28. Public-health interventions included encouragement to report to hospital rapidly after the onset of clinical symptoms, contact tracing for confirmed and suspected cases, and quarantining, monitoring, and restricting the travel of contacts. The mean incubation period of the disease is estimated to be 6.4 days (95% Cl 5.2–7.7). The mean time from onset of clinical symptoms to admission to hospital varied between 3 and 5 days, with longer times earlier in the epidemic. The estimated case fatality rate was 13.2% (9.8–16.8) for patients younger than 60 years and 43.3% (35.2–52.4) for patients aged 60 years or older assuming a parametric γ distribution. A non-parametric method yielded estimates of 6.8% (4.0–9.6) and 55.0% (45.3–64.7), respectively. Case clusters have played an important part in the course of the epidemic. Interpretation Patients’age was strongly associated with outcome. The time between onset of symptoms and admission to hospital did not alter outcome, but shorter intervals will be important to the wider population by restricting the infectious period before patients are placed in quarantine. Published online May 7, 2003 http://image.thelancet.com/extras/03art4453web.pdf

Dual infection with HIV and malaria fuels the spread of both diseases in Sub-Saharan Africa

Mounting evidence has revealed pathological interactions between HIV and malaria in dually infected patients, but the public health implications of the interplay have remained unclear. A transient almost one-log elevation in HIV viral load occurs during febrile malaria episodes; in addition, susceptibility to malaria is enhanced in HIV-infected patients. A mathematical model applied to a setting in Kenya with an adult population of roughly 200,000 estimated that, since 1980, the disease interaction may have been responsible for 8,500 excess HIV infections and 980,000 excess malaria episodes. Co-infection might also have facilitated the geographic expansion of malaria in areas where HIV prevalence is high. Hence, transient and repeated increases in HIV viral load resulting from recurrent co-infection with malaria may be an important factor in promoting the spread of HIV in sub-Saharan Africa.

The global burden of viral hepatitis from 1990 to 2013: findings from the Global Burden of Disease Study 2013

BACKGROUND With recent improvements in vaccines and treatments against viral hepatitis, an improved understanding of the burden of viral hepatitis is needed to inform global intervention strategies. We used data from the Global Burden of Disease (GBD) Study to estimate morbidity and mortality for acute viral hepatitis, and for cirrhosis and liver cancer caused by viral hepatitis, by age, sex, and country from 1990 to 2013. METHODS We estimated mortality using natural history models for acute hepatitis infections and GBDs cause-of-death ensemble model for cirrhosis and liver cancer. We used meta-regression to estimate total cirrhosis and total liver cancer prevalence, as well as the proportion of cirrhosis and liver cancer attributable to each cause. We then estimated cause-specific prevalence as the product of the total prevalence and the proportion attributable to a specific cause. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs). FINDINGS Between 1990 and 2013, global viral hepatitis deaths increased from 0·89 million (95% uncertainty interval [UI] 0·86-0·94) to 1·45 million (1·38-1·54); YLLs from 31·0 million (29·6-32·6) to 41·6 million (39·1-44·7); YLDs from 0·65 million (0·45-0·89) to 0·87 million (0·61-1·18); and DALYs from 31·7 million (30·2-33·3) to 42·5 million (39·9-45·6). In 2013, viral hepatitis was the seventh (95% UI seventh to eighth) leading cause of death worldwide, compared with tenth (tenth to 12th) in 1990. INTERPRETATION Viral hepatitis is a leading cause of death and disability worldwide. Unlike most communicable diseases, the absolute burden and relative rank of viral hepatitis increased between 1990 and 2013. The enormous health loss attributable to viral hepatitis, and the availability of effective vaccines and treatments, suggests an important opportunity to improve public health. FUNDING Bill & Melinda Gates Foundation.

Epidemiological benefits of more-effective tuberculosis vaccines, drugs, and diagnostics

The Bill and Melinda Gates Foundation supports an ambitious portfolio of novel vaccines, drug regimens, and diagnostic tools for tuberculosis (TB). We elicited the expected efficacies and improvements of the novel interventions in discussions with the foundations managing their development. Using an age-structured mathematical model of TB, we explored the potential benefits of novel interventions under development and those not yet in the portfolio, focusing on the WHO Southeast Asia region. Neonatal vaccination with the portfolio vaccine decreases TB incidence by 39% to 52% by 2050. Drug regimens that shorten treatment duration and are efficacious against drug-resistant strains reduce incidence by 10–27%. New diagnostics reduce incidence by 13–42%. A triple combination of a portfolio vaccine, drug regimen, and diagnostics reduces incidence by 71%. A short mass vaccination catch-up campaign, not yet in the portfolio, to augment the triple combination, accelerates the decrease, preventing >30% more cases by 2050 than just the triple combination. New vaccines and drug regimens targeted at the vast reservoir of latently infected people, not in the portfolio, would reduce incidence by 37% and 82%, respectively. The combination of preventive latent therapy and a 2-month drug treatment regimen reduces incidence by 94%. Novel technologies in the pipeline would achieve substantial reductions in TB incidence, but not the Stop TB Partnership target for elimination. Elimination will require new delivery strategies, such as mass vaccination campaigns, and new products targeted at latently infected people.

The epidemiology of hepatitis C virus in Egypt: a systematic review and data synthesis

BackgroundEgypt has the highest prevalence of hepatitis C virus (HCV) in the world, estimated nationally at 14.7%. Our study’s objective was to delineate the evidence on the epidemiology of HCV infection among the different population groups in Egypt, and to draw analytical inferences about the nature of HCV transmission in this country.MethodsWe conducted a systematic review of all data on HCV prevalence and incidence in Egypt following PRISMA guidelines. The main sources of data included PubMed and Embase databases. We also used a multivariate regression model to infer the temporal trend of HCV prevalence among the general population and high risk population in Egypt.ResultsWe identified 150 relevant records, four of which were incidence studies. HCV incidence ranged from 0.8 to 6.8 per 1,000 person-years. Overall, HCV prevalence among pregnant women ranged between 5-15%, among blood donors between 5-25%, and among other general population groups between 0-40%. HCV prevalence among multi-transfused patients ranged between 10-55%, among dialysis patients between 50-90%, and among other high risk populations between 10% and 85%. HCV prevalence varied widely among other clinical populations and populations at intermediate risk. Risk factors appear to be parenteral anti-schistosomal therapy, injections, transfusions, and surgical procedures, among others. Results of our time trend analysis suggest that there is no evidence of a statistically significant decline in HCV prevalence over time in both the general population (p-value: 0.215) and high risk population (p-value: 0.426).ConclusionsEgypt is confronted with an HCV disease burden of historical proportions that distinguishes this nation from others. A massive HCV epidemic at the national level must have occurred with substantial transmission still ongoing today. HCV prevention in Egypt must become a national priority. Policymakers, and public health and medical care stakeholders need to introduce and implement further prevention measures targeting the routes of HCV transmission.

Genital herpes has played a more important role than any other sexually transmitted infection in driving HIV prevalence in Africa

Background Extensive evidence from observational studies suggests a role for genital herpes in the HIV epidemic. A number of herpes vaccines are under development and several trials of the efficacy of HSV-2 treatment with acyclovir in reducing HIV acquisition, transmission, and disease progression have just reported their results or will report their results in the next year. The potential impact of these interventions requires a quantitative assessment of the magnitude of the synergy between HIV and HSV-2 at the population level. Methods and Findings A deterministic compartmental model of HIV and HSV-2 dynamics and interactions was constructed. The nature of the epidemiologic synergy was explored qualitatively and quantitatively and compared to other sexually transmitted infections (STIs). The results suggest a more substantial role for HSV-2 in fueling HIV spread in sub-Saharan Africa than other STIs. We estimate that in settings of high HSV-2 prevalence, such as Kisumu, Kenya, more than a quarter of incident HIV infections may have been attributed directly to HSV-2. HSV-2 has also contributed considerably to the onward transmission of HIV by increasing the pool of HIV positive persons in the population and may explain one-third of the differential HIV prevalence among the cities of the Four City study. Conversely, we estimate that HIV had only a small net impact on HSV-2 prevalence. Conclusions HSV-2 role as a biological cofactor in HIV acquisition and transmission may have contributed substantially to HIV particularly by facilitating HIV spread among the low-risk population with stable long-term sexual partnerships. This finding suggests that prevention of HSV-2 infection through a prophylactic vaccine may be an effective intervention both in nascent epidemics with high HIV incidence in the high risk groups, and in established epidemics where a large portion of HIV transmission occurs in stable partnerships.

Understanding the impact of male circumcision interventions on the spread of HIV in southern Africa.

Background Three randomised controlled trials have clearly shown that circumcision of adult men reduces the chance that they acquire HIV infection. However, the potential impact of circumcision programmes – either alone or in combination with other established approaches – is not known and no further field trials are planned. We have used a mathematical model, parameterised using existing trial findings, to understand and predict the impact of circumcision programmes at the population level. Findings Our results indicate that circumcision will lead to reductions in incidence for women and uncircumcised men, as well as those circumcised, but that even the most effective intervention is unlikely to completely stem the spread of the virus. Without additional interventions, HIV incidence could eventually be reduced by 25–35%, depending on the level of coverage achieved and whether onward transmission from circumcised men is also reduced. However, circumcision interventions can act synergistically with other types of prevention programmes, and if efforts to change behaviour are increased in parallel with the scale-up of circumcision services, then dramatic reductions in HIV incidence could be achieved. In the long-term, this could lead to reduced AIDS deaths and less need for anti-retroviral therapy. Any increases in risk behaviours following circumcision , i.e. ‘risk compensation’, could offset some of the potential benefit of the intervention, especially for women, but only very large increases would lead to more infections overall. Conclusions Circumcision will not be the silver bullet to prevent HIV transmission, but interventions could help to substantially protect men and women from infection, especially in combination with other approaches.

Epidemiology of HIV infection in the Middle East and North Africa.

Objective:The Middle East and North Africa (MENA) region continues to be perceived as a region with very limited HIV epidemiological data, raising many controversies about the status of the epidemic in this part of the world. The objective of this review and synthesis was to address the dearth of strategic interpretable data on HIV in MENA by delineating a data-driven overview of HIV epidemiology in this region. Methods:A comprehensive systematic review of HIV, sexually transmitted infections (STIs) and risk behavior studies in MENA, irrespective of design, was undertaken. Sources of data included Medline for peer-reviewed publications, Google Scholar for other scientific literature published in nonindexed local and regional journals, international organizations reports and databases, country-level reports and database including governmental and nongovernmental organizations publications, as well as various other institutional documents. Results:Over 5000 sources of data related to HIV and STIs were identified and reviewed. The quality of data and nature of study designs varied substantially. There was no evidence for a sustainable HIV epidemic in the general population in any of the MENA countries, except possibly for southern Sudan. The general pattern in different countries in MENA points towards emerging epidemics in high-risk populations including injecting drug users, men who have sex with men (MSM) and to a lesser extent female sex workers, with heterogeneity between countries on the relative role of each of these high-risk groups. Exogenous HIV exposures among nationals linked to travel abroad appeared to be the dominant HIV transmission pattern in a few MENA countries with no evidence for much epidemic or endemic transmission. The role of bridging populations in bridging the HIV infection to the general population was found to be very limited. Conclusion:Although they do not provide complete protection against HIV spread, near universal male circumcision and possibly the prevailing sexually conservative cultural norms seemed to have played so far a protective role in slowing and limiting HIV transmission in MENA relative to other regions. If the existing social and epidemiological context remains largely the same, HIV epidemic transmission is likely to remain confined to high-risk populations and their sexual partners, in addition to exogenous exposures. HIV prevention efforts in this region, which continue to be stymied by stigma associated with HIV/AIDS and related risk behaviors, need to be aggressively expanded with a focus on controlling HIV spread along the contours of risk and vulnerability. There is still a window of opportunity to control further HIV transmission among high-risk groups in MENA that, if missed, may entail a health and socioeconomic burden that the region, in large part, is unprepared for.

Vertical Transmission of Hepatitis C Virus: Systematic Review and Meta-analysis

Updated pooled estimates of vertical hepatitis C (HCV) infection risk to children of HCV RNA–positive mothers ranges between 5.8% and 10.8%, depending on maternal HIV coinfection. Additional risk factors need to be captured and reported by future studies.

No HIV stage is dominant in driving the HIV epidemic in sub-Saharan Africa.

Objective:To estimate the role of each of the HIV progression stages in fueling HIV transmission in sub-Saharan Africa by using the recent measurements of HIV transmission probability per coital per HIV stage in the Rakai study. Methods:A mathematical model, parameterized by empirical data from the Rakai, Masaka, and Four-City studies, was used to estimate the proportion of infections due to each of the HIV stages in two representative epidemics in sub-Saharan Africa. The first setting represents a hyperendemic HIV epidemic (Kisumu, Kenya) whereas the second setting represents a generalized but not hyperendemic HIV epidemic (Yaoundé, Cameroon). Results:We estimate that 17, 51, and 32% of HIV transmissions in Kisumu were due to index cases in their acute, latent, and late stages, respectively. In Yaoundé, the fractions were 25, 44, and 31%. We found that the relative contribution of each stage varied with the epidemic evolution with the acute stage prevailing early on when the infection is concentrated in the high-risk groups with the late stage playing a major role as the epidemic matured and stabilized. The latent stage contribution remained largely stable throughout the epidemic and contributed about half of all transmissions. Conclusion:No HIV stage dominated the epidemical though the latent stage provided the largest contribution. The role of each stage depends on the phase of the epidemic and on the prevailing levels of sexual risk behavior in the populations in which HIV is spreading. These findings may influence the design and implementation of different HIV interventions.