Dr. Rimoin's ongoing work aims to elucidate the epidemiology of monkeypox and other emerging infectious diseases through active disease surveillance in remote regions of central Africa with subsistence hunters and other individuals at who live and work at the human-animal interface and are at high risk for cross species disease transmission. These individuals represent an important sentinel population for monitoring viral disease emergence in a region from which numerous EIDs, including ebola, monkeypox, and marburg have been known to recur.

Human Monkeypox in the Democratic Republic of Congo

Human monkeypox (MPX) is a smallpox-like zoonotic infection that occurs mostly in the rainforests and savannah of central and West Africa. MPX has presumably occurred in sub-Saharan Africa for thousands of years, whenever humans acquired the virus through direct contact with infected animals. However, it was not recognized as a distinct disease until 1970, when the elimination of smallpox from the Democratic Republic of Congo (DRC), formerly known as Zaire, revealed the continued occurrence of a smallpox-like illness in rural areas. An outbreak of MPX in the mid-Western part of the United States in 2003 highlights this virus’s capacity to suddenly emerge from its endemic regions in surprising clusters of infection with an atypical clinical presentation.

Although it is considered to be the most important orthopoxvirus since the eradication of smallpox, MPX disease in humans is poorly understood, its transmission pathways are largely unknown and only a handful of articles have been published in the medical literature describing the disease in its native range. Many factors have hampered research on human MPX infection, including the remote location of cases, war, and lack of field-ready diagnostic tests. The reservoirs for MPX remain largely undefined.

MPX Study #1:
The Epidemiology of Human Monkeypox in the Democratic Republic of Congo

To study the epidemiology of human MPX, we have We are conducting two linked infection/disease burden studies in the Sankuru district of the Kasai Oriental province, a MPX-endemic region of the DRC that has consistently reported the greatest number of MPX cases in the country. The principal aim of these studies is to determine the burden of infection/disease of human MPX. Additional aims include: 1) establish risk factors for acquiring MPX infection; 2) update the current MPX clinical case definition; and 3) enhance local MPX surveillance and laboratory diagnostic capabilities in the DRC.

These clinical surveillance and seroepidemiologic studies will provide the necessary data to determine the MPX infection /disease burden and the associated epidemiology in humans in the DRC and therefore contribute to a better understanding of the public health significance of human MPX. Additionally, these studies will provide essential information for the development of future ecologic studies and vaccine and therapeutic trials for prevention and control of orthopoxviruses in a community setting.

MPX Study 1A:
Active Disease Surveillance for Human Monkeypox in the DRC

In collaboration with the DRC Ministry of Health and the World Health Organization, we are reinforcing active disease surveillance for human MPX throughout the DRC. This project will provide preliminary identification and confirmation of acute cases of MPX occurring in the target region in order to better estimate the burden of incident disease and update the MPX case definition. This project will also improve the MPX disease surveillance system and promote the development of MPX prevention and control methods in the DRC. This study is funded by the National Institutes of Health.

MPX Study 1B:
Seroepidemiology of Human MPX in Endemic Regions of the DRC

We have recently carried out a population-based seroepidemiologic study of 4000 individuals in remote regions of the DRC to estimate present and recent past infection burden of MPX and HIV in the local populations. This study will also provide important information on the prevalence of other infectious diseases in these rural remote populations. This study is funded by the National Institutes of Health.

MPX Study #2:
Development of Rapid Diagnostics for Orthopoxvirus Infections

On June 6th, 2003, the CDC identified the first case of human monkeypox virus (MPV) infection in the Western Hemisphere—two weeks after the first MPV patient was admitted to a hospital and nearly a month after the outbreak first began. This represented the first outbreak of a virulent orthopoxvirus in the U.S. since 1949 – when the last case of smallpox was reported in this country. Although there were no deaths attributed to this particular outbreak, MPV causes substantial disease in Africa where it is associated with a 4-25% mortality rate. Both MPV and its more widely known (and feared) cousin, Variola (VAR), are Select Agents that might be used as biological weapons. There is substantial concern that not all existing stocks of VAR have been accounted for and in the age of genetic engineering, there is also concern that VAR or other virulent orthopoxviruses, such as MPV, could be altered to carry lethal payloads such as toxins or immunomodulatory proteins that would increase virus-induced morbidity and mortality. For these reasons, it is critical to develop effective diagnostics, vaccines, and therapeutics to counter any attempt to deliberately release these biological agents in the United States or abroad.

The goal of this study is to develop rapid and effective OPV-specific (i.e. pan-orthopoxvirus), MPX-specific, and VZV-specific diagnostic reagents with ≥90% specificity and ≥90% sensitivity for all clinically overt cases of infection. In addition, we also want to determine if our rapid serological diagnostic tests will be able to correctly identify subclinical cases of MPV (monkeypox sine eruptione or vaccine-modified asymptomatic MPX infection) in which subjects do not present with MPV skin lesions – a situation in which direct detection of virus may not be feasible.

This study is conducted in collaboration with Dr. Mark Slifka (Oregon Health Sciences University) and Dr. John Fitchen (Najit Technologies) and funded by the National Institutes of Health.

MPX Study #3:
Bringing Genomics to the Rain Forest – The study of Human MPX in the DRC.

In collaboration with Dr. Kate Rubins at the Whitehead Institute/MIT and Dr. David Relman at Stanford University are studying the responses of hospitalized patients with MPX in a rural hospital in the DRC using powerful genomic tools including microarray analysis in order to develop a comprehensive picture of the global gene expression patterns associated with human monkeypox infection. This study is funded by the Keck Foundation.

Emerging Infectious Diseases

Establishing Hunter Cohort to Monitor Cross Species Transmission of Disease

We are a collaborating site in a multi-country study of hunters and their exposure to wildlife blood and body fluids. This study entails accompanying hunters on their hunting trips, noting the locations visited, the techniques used, the species of animal hunted, and any injuries that occurred. The study is aimed at assessing the routes of transmission of animal pathogens and devising ways in which hunters and butchers might be able to reduce their exposure to zoonotic pathogens.

Hunting is common behavior to rural central African villages, particularly in forest areas. Hunted wildlife is used to supplement household nutrition, particularly in areas where commercial supply of domestic animal meat is unavailable. It is also used to supplement income where access to markets or passing traffic permits sale of animal carcasses or smoked meat.

Increasingly, the hunting and butchering of wildlife, and especially of non-human primates, is recognized as a potential risk for both individual and community health. Wild animals are known to be infected with a number of infectious microbes and some of these are harmful to human health. Contact with wildlife, e.g. hunting, can increase the possibility of infection with these agents. Hunters have been found to be infected with microbes such as Simian Foamy Virus (SFV) from hunted primates, and hunting of nonhuman primates infected with SIV is thought to be the pathway that gave raise to HIV.

Hunters are potentially exposed to infections through bites and scratches from live animals, through animal blood contact with wounds when carrying carcasses in backpack baskets, through injuries from knives/machetes during the butchering process, and through the fecal-oral route during and following butchering. However, more information about the degree of interaction of hunters with wild animal carcasses is needed as the risks posed by hunting are currently unquantified. Measuring specific risk points and degree of risk associated with different species/hunting techniques could be used to recommend behavioral changes that would benefit hunters and wider community health.

The objective of this study is to 1) identify microbial pathways during hunting and butchering processes, 2) identify the amount of time people involved in hunting and butchering are exposed to potential infections, 3) identify specific high risk behaviors permitting potential microbial infections, 4) identify hunting and consumption preferences of rural village inhabitants, and 5) identify perceptions of disease origins among rural village inhabitants.

This study is funded by the Global Viral Forecasting Initiative

For additional information on this study:
http://gvfi.org/projects_hunter_contact_study.html

HIV Surveillance in Military Populations in Kinshasa, DRC

This project includes HIV screening of Congolese military, strain typing of HIV found in the cohort, and connecting HIV-positive individuals with local treatment resources.

HIV-1 now causes more global mortality than any other single infectious agent and is the primary cause of death in Africa. Accurate HIV-1 diagnosis in the context of counseling and effective prevention programs, access to treatment, and effective preventive vaccines are the central tools for addressing the pandemic. There is scant published information on the prevalence of HIV in the Democratic Republic of Congo and no information available on the prevalence of HIV in Congolese military. This study, run in collaboration with the Congolese military, will provide critical information to understand the scope of infection and develop effective prevention and control programs in the DRC.

This study is funded by DHAPP and is a part of a larger multi-country study of HIV in African Militaries.

Monitoring Select Populations for Emerging Zoonotic Infections

The majority of emerging infectious diseases (EIDs) have animal origins including: Ebola, monkeypox, plague, SARS, West Nile virus, and most recently, avian influenza. The entry of novel animal diseases into human populations can have a devastating impact on global health, economy, and security. There are currently no effective systems in place to monitor and stop zoonotic EIDs before they emerge. This study utilizes a novel multi-disciplinary approach to monitoring for the emergence of such diseases in individuals who are at the nexus of animal and human interaction. This study will focus on populations of individuals in the Democratic Republic of Congo that are regularly exposed to wild animals (bats, non-human primates, rodents, etc.), due to their reliance on these animals for a source of food. Individuals in this population will be enrolled into a study aimed at determining the presence of zoonotic infection. To that end, serologic, microarray and PCR-based techniques will be used to screen the collected blood samples for infection with known and novel viruses. This may lead to an understanding of which zoonotic microorganisms have the potential to infect, cause disease, and spread in human populations.

Avian Influenza Project

Wild birds have also often been implicated in the spread of numerous diseases to humans leading to global pandemics. In particular, migrating birds, which have the potential to disseminate diseases over a wide geographic area, are believed to be currently spreading avian influenza viruses across the globe. Influenza A viruses are perpetuated in wild birds that act as a source of infection for the disease. The human aspect of this study is to investigate the potential for wild birds to infect humans with avian influenza viruses. To investigate this possibility, this study will collect blood specimens from individuals with substantial contact with wild birds, professional and enthusiast bird-handlers in North America. These blood samples will then be analyzed for evidence of past infection with avian influenza virus strains. Concomitantly, samples will be collected from wild birds in North America to determine strains of avian influenza that are circulating in avian populations.

In collaboration with the Center for Tropical Research at UCLA, we integrating the biological data obtained from avian and human populations with the latest methodologies in remote sensing, molecular biology and near real time surveillance. It is novel in that we are studying both an avian and human disease over a broad scale. This research has the potential to provide some of the first data on how habitat changes affect the prevalence of disease in birds, and additionally provide data on the evolutionary relationship of viral diseases in migratory avifauna. These data provided by spatially refined satellite remote sensing will establish which ecological and land use characteristics best correlate with disease prevalence. These results will be used to develop models that will aid in predicting how future anthropogenic ecological changes may affect disease prevalence and transmission. Importantly, the sampling methodology also provides for an extensive avian surveillance network for avian influenza across North America, Mexico and portions of Central and South America involving over 400 bird-banding stations that will generate a large volume of samples annually.