Martial L. Ndeffo-Mbah

Strategies for containing Ebola in West Africa.

The ongoing Ebola outbreak poses an alarming risk to the countries of West Africa and beyond. To assess the effectiveness of containment strategies, we developed a stochastic model of Ebola transmission between and within the general community, hospitals, and funerals, calibrated to incidence data from Liberia. We find that a combined approach of case isolation, contact-tracing with quarantine, and sanitary funeral practices must be implemented with utmost urgency in order to reverse the growth of the outbreak. As of 19 September, under status quo, our model predicts that the epidemic will continue to spread, generating a predicted 224 (134 to 358) daily cases by 1 December, 280 (184 to 441) by 15 December, and 348 (249 to 545) by 30 December. A combination of hygienic practices could feasibly check Ebola within 6 months. Recharging Ebola mitigation measures Effective drugs and vaccines for Ebola virus are not available, so what can be done? Pandey et al. used a mathematical model to analyze transmission in different scenarios: the community, hospitals, and at funerals. Achieving full compliance with any single control measure, such as case isolation, is impossible under prevailing conditions. However, with a minimum of 60% compliance, a combination of case isolation, hygienic burial, and contact tracing could reduce daily case numbers to single figures in 5 to 6 months. Success will also require persistence and sensitivity to local customs. Science, this issue p. 991

Global burden of HIV, viral hepatitis, and tuberculosis in prisoners and detainees

The prison setting presents not only challenges, but also opportunities, for the prevention and treatment of HIV, viral hepatitis, and tuberculosis. We did a comprehensive literature search of data published between 2005 and 2015 to understand the global epidemiology of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV), and tuberculosis in prisoners. We further modelled the contribution of imprisonment and the potential impact of prevention interventions on HIV transmission in this population. Of the estimated 10·2 million people incarcerated worldwide on any given day in 2014, we estimated that 3·8% have HIV (389 000 living with HIV), 15·1% have HCV (1 546 500), 4·8% have chronic HBV (491 500), and 2·8% have active tuberculosis (286 000). The few studies on incidence suggest that intraprison transmission is generally low, except for large-scale outbreaks. Our model indicates that decreasing the incarceration rate in people who inject drugs and providing opioid agonist therapy could reduce the burden of HIV in this population. The prevalence of HIV, HCV, HBV, and tuberculosis is higher in prison populations than in the general population, mainly because of the criminalisation of drug use and the detention of people who use drugs. The most effective way of controlling these infections in prisoners and the broader community is to reduce the incarceration of people who inject drugs.

Effect of Ebola Progression on Transmission and Control in Liberia

BACKGROUND The Ebola outbreak that is sweeping across West Africa is the largest, most volatile, and deadliest Ebola epidemic ever recorded. Liberia is the most profoundly affected country, with more than 3500 infections and 2000 deaths recorded in the past 3 months. OBJECTIVE To evaluate the contribution of disease progression and case fatality on transmission and to examine the potential for targeted interventions to eliminate the disease. DESIGN Stochastic transmission model that integrates epidemiologic and clinical data on incidence and case fatality, daily viral load among survivors and nonsurvivors evaluated on the basis of the 2000-2001 outbreak in Uganda, and primary data on contacts of patients with Ebola in Liberia. SETTING Montserrado County, Liberia, July to September 2014. MEASUREMENTS Ebola incidence and case-fatality records from 2014 Liberian Ministry of Health and Social Welfare. RESULTS The average number of secondary infections generated throughout the entire infectious period of a single infected case, R, was estimated as 1.73 (95% CI, 1.66 to 1.83). There was substantial stratification between survivors (RSurvivors), for whom the estimate was 0.66 (CI, 0.10 to 1.69), and nonsurvivors (RNonsurvivors), for whom the estimate was 2.36 (CI, 1.72 to 2.80). The nonsurvivors had the highest risk for transmitting the virus later in the course of disease progression. Consequently, the isolation of 75% of infected individuals in critical condition within 4 days from symptom onset has a high chance of eliminating the disease. LIMITATION Projections are based on the initial dynamics of the epidemic, which may change as the outbreak and interventions evolve. CONCLUSION These results underscore the importance of isolating the most severely ill patients with Ebola within the first few days of their symptomatic phase. PRIMARY FUNDING SOURCE National Institutes of Health.

Effects of Response to 2014-2015 Ebola Outbreak on Deaths from Malaria, HIV/AIDS, and Tuberculosis, West Africa

Reduced access to healthcare during the outbreak substantially increased mortality rates from other diseases.

Epidemiological and Viral Genomic Sequence Analysis of the 2014 Ebola Outbreak Reveals Clustered Transmission

Using Ebolavirus genomic and epidemiological data, we conducted the first joint analysis in which both data types were used to fit dynamic transmission models for an ongoing outbreak. Our results indicate that transmission is clustered, highlighting a potential bias in medical demand forecasts, and provide the first empirical estimate of underreporting.

Quantitative analyses and modelling to support achievement of the 2020 goals for nine neglected tropical diseases

Quantitative analysis and mathematical models are useful tools in informing strategies to control or eliminate disease. Currently, there is an urgent need to develop these tools to inform policy to achieve the 2020 goals for neglected tropical diseases (NTDs). In this paper we give an overview of a collection of novel model-based analyses which aim to address key questions on the dynamics of transmission and control of nine NTDs: Chagas disease, visceral leishmaniasis, human African trypanosomiasis, leprosy, soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis and trachoma. Several common themes resonate throughout these analyses, including: the importance of epidemiological setting on the success of interventions; targeting groups who are at highest risk of infection or re-infection; and reaching populations who are not accessing interventions and may act as a reservoir for infection,. The results also highlight the challenge of maintaining elimination ‘as a public health problem’ when true elimination is not reached. The models elucidate the factors that may be contributing most to persistence of disease and discuss the requirements for eventually achieving true elimination, if that is possible. Overall this collection presents new analyses to inform current control initiatives. These papers form a base from which further development of the models and more rigorous validation against a variety of datasets can help to give more detailed advice. At the moment, the models’ predictions are being considered as the world prepares for a final push towards control or elimination of neglected tropical diseases by 2020.

Ebola Vaccination: If Not Now, When?

Ebola virus disease causes severe hemorrhagic fever, with a case-fatality rate of 50% to 90% (1). The ongoing epidemic in West Africa is the largest Ebola outbreak ever recorded and is rapidly crossing borders. The relentless epidemiologic trajectory and geographic dissemination represent a public health crisis that shows no signs of diminishing under current efforts. We believe that the time to deploy Ebola vaccines is now, as advocated in recent statements by the World Health Organization. Ebola arises sporadically via zoonosis from fruit bats (the natural reservoir) to humans, often through great apes. Human-to-human transmission occurs primarily through contact with infected body fluids. This transmission route puts health care workers, family members, and persons preparing bodies for traditional funerals at high risk for the disease (1). Although no Ebola vaccines are currently licensed, many candidates have been developed in the past decade. A DNA vaccine has been shown to be safe and immunogenic in a phase 1 clinical trial (2). In addition, a therapeutic vaccine based on recombinant vesicular stomatitis viruses (rVSVs) expressing Ebola virus surface glycoprotein was found to confer prophylactic and postexposure protection in nonhuman primates (3). Despite the promise of these and other Ebola vaccine candidates, none have advanced to late-stage human trials and licensure. The challenge in this process has been the inability to evaluate vaccine efficacy in human populations given the sporadic nature of Ebola outbreaks. For unique circumstances, such as those where conventional efficacy trials are not feasible, the U.S. Food and Drug Administration has created the animal rule, which states that licensure can be approved on the basis of animal model studies that replicate human disease combined with safety and immunologic data from humans (4). Nonhuman primates serve as the gold standard for animal models of Ebola infection and have been used to test Ebola vaccine candidates, with promising results (Table). Alternate vaccine candidates have specific properties that must be taken into consideration for selection of the ideal vaccine under given circumstances. For example, one that requires several weeks to develop immunogenicity, such as the recombinant adenovirusbased DNA vaccine, could be appropriate in high-risk settings not currently affected by an Ebola outbreak (2). Similarly, a vaccine that remains viable at ambient temperatures, such as the Ebola subunit vaccine (5), could be stockpiled as part of a preparedness strategy. In contrast, the species-specific properties of a recombinant cytomegalovirus vaccine make it a candidate for wildlife vaccination in Ebola-endemic areas (6). Although a wildlife vaccination strategy would not be the focus of a containment strategy to control an outbreak already in a human population, it may be a component of a longer-term strategy to reduce Ebola zoonosis. With regard to the current outbreak, given that the rVSV vaccine has shown efficacy in eliciting both prophylactic and postexposure protection (3), it is probably the vaccine of choice for persons in a high-risk setting who may have already been exposed. The rVSV vaccine has also been found to be effective in primates infected with simian immunodeficiency virus (7) and may therefore be particularly well-suited for use in populations with a high prevalence of HIV. We believe that the safety risks of vaccines, particularly those found to be safe in phase 1 clinical trials, are probably negligible compared with the risks faced by health care workers in communities where the highly virulent Ebola virus is currently circulating. Table. Viable Ebola Vaccine Candidates Possible strategies could include the vaccination of health care workers in high-risk regions. Ideally, the vaccine would be administered as soon as possible and before exposure. Nevertheless, the postexposure efficacy of the rVSV vaccine is reassuring in the context of the current outbreak, where health care workers may already have been inadvertently exposed. Another strategy that would complement the vaccination of health care workers is postexposure ring vaccination and quarantine of those who have probably been exposed to the virus, including vaccinating close contacts of infected persons. The rVSV vaccine would be promising for both of these target groups given its prophylactic and postexposure efficacies compared with other vaccine candidates that are slower to elicit a protective immunologic response. Epidemiologic modeling can facilitate the optimization of such vaccination strategies when vaccine supply is limited and production has to be scaled up. Primarily, an Ebola vaccine could mitigate disease transmission and protect health care workers, thus enabling an effective medical and epidemiologic response in affected areas. Secondarily, the emergency deployment of an Ebola vaccine may also serve as a source of data that could be used to further demonstrate efficacy and waning properties that are fundamental to informing preparedness strategies to prevent future outbreaks. Vaccination alone is no panacea. Cultural and socioeconomic factors and suspicion of Western medical approaches complicate all medical interventions. Epidemiologic practices, such as trace-back investigations to identify and quarantine persons exposed to Ebola, are pivotal to controlling spread. Such control methods require trained personnel on the ground in even the most remote locations. Given that nosocomial transmission has contributed substantially to past Ebola outbreaks (1), it is also imperative to integrate vaccination with nosocomial contact precautions and quarantining. Although vaccine production, transport, and cost are undeniable logistical challenges to any vaccination strategy, the resources required to implement vaccination should be made available by the international community given the magnitude of the threat that the current Ebola outbreak poses to countries in which transmission is occurring and to which it may spread. Even from a pragmatic perspective, it is in the interest of the international community to assist West Africa in containing the Ebola outbreak. Curtailing an outbreak is always easier in its earliest stages than after it has disseminated geographically. That window of opportunity may be rapidly closing.

A Cost-Effectiveness Tool for Informing Policies on Zika Virus Control

Background As Zika virus continues to spread, decisions regarding resource allocations to control the outbreak underscore the need for a tool to weigh policies according to their cost and the health burden they could avert. For example, to combat the current Zika outbreak the US President requested the allocation of

National- and state-level impact and cost-effectiveness of nonavalent HPV vaccination in the United States

1.8 billion from Congress in February 2016. Methodology/Principal Findings Illustrated through an interactive tool, we evaluated how the number of Zika cases averted, the period during pregnancy in which Zika infection poses a risk of microcephaly, and probabilities of microcephaly and Guillain-Barré Syndrome (GBS) impact the cost at which an intervention is cost-effective. From Northeast Brazilian microcephaly incidence data, we estimated the probability of microcephaly in infants born to Zika-infected women (0.49% to 2.10%). We also estimated the probability of GBS arising from Zika infections in Brazil (0.02% to 0.06%) and Colombia (0.08%). We calculated that each microcephaly and GBS case incurs the loss of 29.95 DALYs and 1.25 DALYs per case, as well as direct medical costs for Latin America and the Caribbean of

Spatial heterogeneity in projected leprosy trends in India

91,102 and