Neglected tropical diseases in Central America and Panama: Review of their prevalence,populations at risk and impact on regional development

A review of the literature since 2009 reveals a staggering health and economic burden resulting from neglected tropical diseases in Panama and the six countries of Central America (referred to collectively here as ‘Central America’). Particularly at risk are the 10.2 million people in the region who live on less than $2 per day, mostly in Guatemala, Honduras, Nicaragua and El Salvador. Indigenous populations are especially vulnerable to neglected tropical diseases. Currently, more than 8 million Central American children require mass drug treatments annually (or more frequently) for their intestinal helminth infections, while vector-borne diseases are widespread. Among the vector-borne parasitic infections, almost 40% of the population is at risk for malaria (mostly Plasmodium vivax infection), more than 800,000 people live with Chagas disease, and up to 39,000 people have cutaneous leishmaniasis. In contrast, an important recent success story is the elimination of onchocerciasis from Central America. Dengue is the leading arbovirus infection with 4–5 million people affected annually and hantavirus is an important rodent-borne viral neglected tropical disease. The leading bacterial neglected tropical diseases include leptospirosis and trachoma, for which there are no disease burden estimates. Overall there is an extreme dearth of epidemiological data on neglected tropical diseases based on active surveillance as well as estimates of their economic impact. Limited information to date, however, suggests that neglected tropical diseases are a major hindrance to the region’s economic development, in both the most impoverished Central American countries listed above, as well as for Panama and Costa Rica where a substantial (but largely hidden) minority of people live in extreme poverty.     

The neglected tropical diseases of Latin America and the Caribbean: a review of disease burden and distribution and a roadmap for control and elimination

The neglected tropical diseases (NTDs) represent some of the most common infections of the poorest people living in the Latin American and Caribbean region (LAC). Because they primarily afflict the disenfranchised poor as well as selected indigenous populations and people of African descent, the NTDs in LAC are largely forgotten diseases even though their collective disease burden may exceed better known conditions such as of HIV/AIDS, tuberculosis, or malaria. Based on their prevalence and healthy life years lost from disability, hookworm infection, other soil-transmitted helminth infections, and Chagas disease are the most important NTDs in LAC, followed by dengue, schistosomiasis, leishmaniasis, trachoma, leprosy, and lymphatic filariasis. On the other hand, for some important NTDs, such as leptospirosis and cysticercosis, complete disease burden estimates are not available. The NTDs in LAC geographically concentrate in 11 different sub-regions, each with a distinctive human and environmental ecology. In the coming years, schistosomiasis could be eliminated in the Caribbean and transmission of lymphatic filariasis and onchocerciasis could be eliminated in Latin America. However, the highest disease burden NTDs, such as Chagas disease, soil-transmitted helminth infections, and hookworm and schistosomiasis co-infections, may first require scale-up of existing resources or the development of new control tools in order to achieve control or elimination. Ultimately, the roadmap for the control and elimination of the more widespread NTDs will require an inter-sectoral approach that bridges public health, social services, and environmental interventions.     

Neglected Tropical Diseases in Sub-Saharan Africa: Review of Their Prevalence,Distribution, and Disease Burden

The neglected tropical diseases (NTDs) are the most common conditions affecting the poorest 500 million people living in sub-Saharan Africa (SSA), and together produce a burden of disease that may be equivalent to up to one-half of SSA''s malaria disease burden and more than double that caused by tuberculosis. Approximately 85% of the NTD disease burden results from helminth infections. Hookworm infection occurs in almost half of SSA''s poorest people, including 40–50 million school-aged children and 7 million pregnant women in whom it is a leading cause of anemia. Schistosomiasis is the second most prevalent NTD after hookworm (192 million cases), accounting for 93% of the world''s number of cases and possibly associated with increased horizontal transmission of HIV/AIDS. Lymphatic filariasis (46–51 million cases) and onchocerciasis (37 million cases) are also widespread in SSA, each disease representing a significant cause of disability and reduction in the region''s agricultural productivity. There is a dearth of information on Africa''s non-helminth NTDs. The protozoan infections, human African trypanosomiasis and visceral leishmaniasis, affect almost 100,000 people, primarily in areas of conflict in SSA where they cause high mortality, and where trachoma is the most prevalent bacterial NTD (30 million cases). However, there are little or no data on some very important protozoan infections, e.g., amebiasis and toxoplasmosis; bacterial infections, e.g., typhoid fever and non-typhoidal salmonellosis, the tick-borne bacterial zoonoses, and non-tuberculosis mycobaterial infections; and arboviral infections. Thus, the overall burden of Africa''s NTDs may be severely underestimated. A full assessment is an important step for disease control priorities, particularly in Nigeria and the Democratic Republic of Congo, where the greatest number of NTDs may occur.     

Historical Perspectives on the Epidemiology of Human Chagas Disease in Texas and Recommendations for Enhanced Understanding of Clinical Chagas Disease in the Southern United States

Chagas disease (Trypanosoma cruzi infection) has recently been identified as an important neglected tropical disease in the United States. Anecdotally referred to as a “silent killer,” it leads to the development of potentially fatal cardiac disease in approximately 30% of those infected. In an attempt to better understand the potential of Chagas disease as a significant underlying cause of morbidity in Texas, we performed a historical literature review to assess disease burden. Human reports of triatomine bites and disease exposure were found to be prevalent in Texas. Despite current beliefs that Chagas disease is a recently emerging disease, we report historical references dating as far back as 1935. Both imported cases and autochthonous transmission contribute to the historical disease burden in Texas. We end by discussing the current knowledge gaps, and recommend priorities for advancing further epidemiologic studies and their policy implications.     

Effect of clinician information sessions on diagnostic testing for Chagas disease

BackgroundChagas disease is a potentially life-threatening neglected disease of poverty that is endemic in continental Latin America. Caused by Trypanosoma cruzi (T. cruzi), it is one of six parasitic diseases in the United States targeted by the Centers for Disease Control as a public health problem in need of action. An estimated 300,000 people are infected with T. cruzi in the United States (US). Although its morbidity, mortality and economic burden are high, awareness of Chagas disease is lacking among many healthcare providers in the US. The purpose of this analysis is to determine if the number of diagnostic tests performed at a community health center serving an at-risk population for Chagas disease increased after information sessions. A secondary aim was to determine if there was a difference by provider type, i.e., nurse practitioner vs. physician, or by specialty in the number of patients screened.Methodology/Principal findingsWe conducted a retrospective data analysis of the number of Chagas serology tests performed at a community health center before and after information sessions for clinicians. A time series analysis was conducted focusing on the Adult and Family Medicine Departments at East Boston Neighborhood Health Center (EBNHC). Across all departments there were 1,957 T. cruzi tests performed before the sessions vs. 2,623 after the sessions. Interrupted time series analysis across departments indicated that testing volume was stable over time prior to the sessions (pre-period slope = +4.1 per month; p = 0.12), followed by an immediate shift after the session (+51.6; p = 0.03), while testing volume remained stable over time after the session (post-period slope = -6.0 per month; p = 0.11).Conclusion/SignificanceIn this study, Chagas testing increased after information sessions. Clinicians who began testing their patients for Chagas disease after learning of the importance of this intervention added an extra, potentially time-consuming task to their already busy workdays without external incentives or recognition.     

Streptococcal Superantigen,Mitogenic Factor,and Pyrogenic Exotoxin B Expressed by Streptococcus pyogenes

Abstract

Streptococcus pyogenes is a Gram-positive human bacterial pathogen that causes pharyngitis, tonsillitis, skin infections (impetigo, erysipelis, and other forms of pyoderma), acute rheumatic fever (ARF), scarlet fever (SF), poststreptococcal glomerulonephritis (PSGN), a streptococcal toxic shock syndrome (STSS), and necrotizing fasciitis. These infections are some of the most economically and medically important conditions that affect humans. For example, globally, ARF is the most common cause of pediatric heart disease. It is estimated that in India more than six million school-aged children suffer from rheumatic heart disease (1). In the United States, “sore throat” is the third most common reason for physician office visits and S. pyogenes is recovered from about 30% of children with this complaint (2). It has been estimated that there are 25–35 million cases of streptococcal pharyngitis per year in the United States, and these infections cause 1–2 billion dollars per year in direct health care costs (3,4). Although the continued great morbidity and mortality caused by S. pyogenes in developing nations, the significant health care financial burden attributable to group A streptococci in the United States, and increasing levels of antibiotic resistance (5), have highlighted the need for a fuller understanding of the molecular pathogenesis of streptococcal infection, it has been the relatively recent intercontinental increase in streptococcal disease frequency and severity (6,7) that has resulted in renewed interest in S. pyogenes virulence factors and host-parasite interactions.     

Prevalence of Chagas Disease in Latin-American Migrants Living in Europe: A Systematic Review and Meta-analysis

Background

Few studies have assessed the burden of Chagas disease in non-endemic countries and most of them are based on prevalence estimates from Latin American (LA) countries that likely differ from the prevalence in migrants living in Europe. The aim of this study was to systematically review the existing data informing current understanding of the prevalence of Chagas disease in LA migrants living in European countries.

Methods

We conducted a systematic review and meta-analysis of studies reporting prevalence of Chagas disease in European countries belonging to the European Union (EU) before 2004 in accordance with the MOOSE guidelines and based on the database sources MEDLINE and Global Health. No restrictions were placed on study date, study design or language of publication. The pooled prevalence was estimated using random effect models based on DerSimonian & Laird method.

Results

We identified 18 studies conducted in five European countries. The random effect pooled prevalence was 4.2% (95%CI:2.2-6.7%); and the heterogeneity of Chagas disease prevalence among studies was high (I2 = 97%,p<0.001). Migrants from Bolivia had the highest prevalence of Chagas disease (18.1%, 95%CI:13.9–22.7%).

Conclusions

Prevalence of Chagas in LA migrants living in Europe is high, particularly in migrants from Bolivia and Paraguay. Data are highly heterogeneous dependent upon country of origin and within studies of migrants from the same country of origin. Country-specific prevalence differs from the estimates available from LA countries. Our meta-analysis provides prevalence estimates of Chagas disease that should be used to estimate the burden of disease in European countries.     

Neglected Tropical Diseases among the Association of Southeast Asian Nations (ASEAN): Overview and Update

The ten member states of the Association of Southeast Asian Nations (ASEAN) constitute an economic powerhouse, yet these countries also harbor a mostly hidden burden of poverty and neglected tropical diseases (NTDs). Almost 200 million people live in extreme poverty in ASEAN countries, mostly in the low or lower middle-income countries of Indonesia, the Philippines, Myanmar, Viet Nam, and Cambodia, and many of them are affected by at least one NTD. However, NTDs are prevalent even among upper middle-income ASEAN countries such as Malaysia and Thailand, especially among the indigenous populations. The three major intestinal helminth infections are the most common NTDs; each helminthiasis is associated with approximately 100 million infections in the region. In addition, more than 10 million people suffer from either liver or intestinal fluke infections, as well as schistosomiasis and lymphatic filariasis (LF). Intestinal protozoan infections are widespread, while leishmaniasis has emerged in Thailand, and zoonotic malaria (Plasmodium knowlesi infection) causes severe morbidity in Malaysia. Melioidosis has emerged as an important bacterial NTD, as have selected rickettsial infections, and leptospirosis. Leprosy, yaws, and trachoma are still endemic in focal areas. Almost 70 million cases of dengue fever occur annually in ASEAN countries, such that this arboviral infection is now one of the most common and economically important NTDs in the region. A number of other arboviral and zoonotic viral infections have also emerged, including Japanese encephalitis; tick-borne viral infections; Nipah virus, a zoonosis present in fruit bats; and enterovirus 71 infection. There are urgent needs to expand surveillance activities in ASEAN countries, as well as to ensure mass drug administration is provided to populations at risk for intestinal helminth and fluke infections, LF, trachoma, and yaws. An ASEAN Network for Drugs, Diagnostics, Vaccines, and Traditional Medicines Innovation provides a policy framework for the development of new control and elimination tools. Together with prominent research institutions and universities, the World Health Organization (WHO), and its regional offices, these organizations could implement important public health improvements through NTD control and elimination in the coming decade.     

Epidemiology of Chagas disease in non-endemic countries: the role of international migration

Human infection with the protozoa Trypanosoma cruzi extends through North, Central, and South America, affecting 21 countries. Most human infections in the Western Hemisphere occur through contact with infected bloodsucking insects of the triatomine species. As T. cruzi can be detected in the blood of untreated infected individuals, decades after infection took place; the infection can be also transmitted through blood transfusion and organ transplant, which is considered the second most common mode of transmission for T. cruzi. The third mode of transmission is congenital infection. Economic hardship, political problems, or both, have spurred migration from Chagas endemic countries to developed countries. The main destination of this immigration is Australia, Canada, Spain, and the United States. In fact, human infection through blood or organ transplantation, as well as confirmed or potential cases of congenital infections has been described in Spain and in the United States. Estimates reported here indicates that in Australia in 2005-2006, 1067 of the 65,255 Latin American immigrants (16 per 1000) may be infected with T. cruzi, and in Canada, in 2001, 1218 of the 131,135 immigrants (9 per 1000) whose country of origin was identified may have been also infected. In Spain, a magnet for Latin American immigrants since the 2000, 6141 of 38,777 to 339,954 [corrected] legal immigrants in 2003 (25 per 1000), could be infected. In the United States, 56,028 to 357,205 of the 7,20 million, legal immigrants (8 to 50 per 1000), depending on the scenario, from the period 1981-2005 may be infected with T. cruzi. On the other hand, 33,193 to 336,097 of the estimated 5,6 million undocumented immigrants in 2000 (6 to 59 per 1000) could be infected. Non endemic countries receiving immigrants from the endemic ones should develop policies to protect organ recipients from T. cruzi infection, prevent tainting the blood supply with T. cruzi, and implement secondary prevention of congenital Chagas disease.     

Neglected tropical diseases of the Middle East and North Africa: review of their prevalence, distribution, and opportunities for control

The neglected tropical diseases (NTDs) are highly endemic but patchily distributed among the 20 countries and almost 400 million people of the Middle East and North Africa (MENA) region, and disproportionately affect an estimated 65 million people living on less than US$2 per day. Egypt has the largest number of people living in poverty of any MENA nation, while Yemen has the highest prevalence of people living in poverty. These two nations stand out for having suffered the highest rates of many NTDs, including the soil-transmitted nematode infections, filarial infections, schistosomiasis, fascioliasis, leprosy, and trachoma, although they should be recognized for recent measures aimed at NTD control. Leishmaniasis, especially cutaneous leishmaniasis, is endemic in Syria, Iran, Iraq, Libya, Morocco, and elsewhere in the region. Both zoonotic (Leishmania major) and anthroponotic (Leishmania tropica) forms are endemic in MENA in rural arid regions and urban regions, respectively. Other endemic zoonotic NTDs include cystic echinococcosis, fascioliasis, and brucellosis. Dengue is endemic in Saudi Arabia, where Rift Valley fever and Alkhurma hemorrhagic fever have also emerged. Great strides have been made towards elimination of several endemic NTDs, including lymphatic filariasis in Egypt and Yemen; schistosomiasis in Iran, Morocco, and Oman; and trachoma in Morocco, Algeria, Iran, Libya, Oman, Saudi Arabia, Tunisia, and the United Arab Emirates. A particularly noteworthy achievement is the long battle waged against schistosomiasis in Egypt, where prevalence has been brought down by regular praziquantel treatment. Conflict and human and animal migrations are key social determinants in preventing the control or elimination of NTDs in the MENA, while local political will, strengthened international and intersectoral cooperative efforts for surveillance, mass drug administration, and vaccination are essential for elimination.     

Integrated control of Chagas disease for its elimination as public health problem - A Review

Chagas disease or American trypanosomiasis is, together with geohelminths, the neglected disease that causes more loss of years of healthy life due to disability in Latin America. Chagas disease, as determined by the factors and determinants, shows that different contexts require different actions, preventing new cases or reducing the burden of disease. Control strategies must combine two general courses of action including prevention of transmission to prevent the occurrence of new cases (these measures are cost effective), as well as opportune diagnosis and treatment of infected individuals in order to prevent the clinical evolution of the disease and to allow them to recuperate their health. All actions should be implemented as fully as possible and with an integrated way, to maximise the impact. Chagas disease cannot be eradicated due because of the demonstrated existence of infected wild triatomines in permanent contact with domestic cycles and it contributes to the occurrence of at least few new cases. However, it is possible to interrupt the transmission of Trypanosoma cruzi in a large territory and to eliminate Chagas disease as a public health problem with a dramatic reduction of burden of the disease.     

A Tractable Experimental Model for Study of Human and Animal Scabies

Background

Scabies is a parasitic skin infestation caused by the burrowing mite Sarcoptes scabiei. It is common worldwide and spreads rapidly under crowded conditions, such as those found in socially disadvantaged communities of Indigenous populations and in developing countries. Pruritic scabies lesions facilitate opportunistic bacterial infections, particularly Group A streptococci. Streptococcal infections cause significant sequelae and the increased community streptococcal burden has led to extreme levels of acute rheumatic fever and rheumatic heart disease in Australia''s Indigenous communities. In addition, emerging resistance to currently available therapeutics emphasizes the need to identify potential targets for novel chemotherapeutic and/or immunological intervention. Scabies research has been severely limited by the availability of parasites, and scabies remains a truly neglected infectious disease. We report development of a tractable model for scabies in the pig, Sus domestica.

Methodology/Principal Findings

Over five years and involving ten independent cohorts, we have developed a protocol for continuous passage of Sarcoptes scabiei var. suis. To increase intensity and duration of infestation without generating animal welfare issues we have optimised an immunosuppression regimen utilising daily oral treatment with 0.2mg/kg dexamethasone. Only mild, controlled side effects are observed, and mange infection can be maintained indefinitely providing large mite numbers (>6000 mites/g skin) for molecular-based research on scabies. In pilot experiments we explore whether any adaptation of the mite population is reflected in genetic changes. Phylogenetic analysis was performed comparing sets of genetic data obtained from pig mites collected from naturally infected pigs with data from pig mites collected from the most recent cohort.

Conclusions/Significance

A reliable pig/scabies animal model will facilitate in vivo studies on host immune responses to scabies including the relations to the associated bacterial pathogenesis and more detailed studies of molecular evolution and host adaption. It is a most needed tool for the further investigation of this important and widespread parasitic disease.     

Optimization of a Bioluminescence Resonance Energy Transfer-Based Assay for Screening of <Emphasis Type="Italic">Trypanosoma cruzi</Emphasis> Protein/Protein Interaction Inhibitors

Chagas disease, a parasitic disease caused by Trypanosoma cruzi, is a major public health burden in poor rural populations of Central and South America and a serious emerging threat outside the endemic region, since the number of infections in non-endemic countries continues to rise. In order to develop more efficient anti-trypanosomal treatments to replace the outdated therapies, new molecular targets need to be explored and new drugs discovered. Trypanosoma cruzi has distinctive structural and functional characteristics with respect to the human host. These exclusive features could emerge as interesting drug targets. In this work, essential and differential protein–protein interactions for the parasite, including the ribosomal P proteins and proteins involved in mRNA processing, were evaluated in a bioluminescence resonance energy transfer-based assay as a starting point for drug screening. Suitable conditions to consider using this simple and robust methodology to screening compounds and natural extracts able to inhibit protein–protein interactions were set in living cells and lysates.     

Global Morbidity and Mortality of Leptospirosis: A Systematic Review

BackgroundLeptospirosis, a spirochaetal zoonosis, occurs in diverse epidemiological settings and affects vulnerable populations, such as rural subsistence farmers and urban slum dwellers. Although leptospirosis is a life-threatening disease and recognized as an important cause of pulmonary haemorrhage syndrome, the lack of global estimates for morbidity and mortality has contributed to its neglected disease status.Conclusions/SignificanceLeptospirosis is among the leading zoonotic causes of morbidity worldwide and accounts for numbers of deaths, which approach or exceed those for other causes of haemorrhagic fever. Highest morbidity and mortality were estimated to occur in resource-poor countries, which include regions where the burden of leptospirosis has been underappreciated.     

Chagas Disease Risk in Texas

Background

Chagas disease, caused by Trypanosoma cruzi, remains a serious public health concern in many areas of Latin America, including México. It is also endemic in Texas with an autochthonous canine cycle, abundant vectors (Triatoma species) in many counties, and established domestic and peridomestic cycles which make competent reservoirs available throughout the state. Yet, Chagas disease is not reportable in Texas, blood donor screening is not mandatory, and the serological profiles of human and canine populations remain unknown. The purpose of this analysis was to provide a formal risk assessment, including risk maps, which recommends the removal of these lacunae.

Methods and Findings

The spatial relative risk of the establishment of autochthonous Chagas disease cycles in Texas was assessed using a five–stage analysis. 1. Ecological risk for Chagas disease was established at a fine spatial resolution using a maximum entropy algorithm that takes as input occurrence points of vectors and environmental layers. The analysis was restricted to triatomine vector species for which new data were generated through field collection and through collation of post–1960 museum records in both México and the United States with sufficiently low georeferenced error to be admissible given the spatial resolution of the analysis (1 arc–minute). The new data extended the distribution of vector species to 10 new Texas counties. The models predicted that Triatoma gerstaeckeri has a large region of contiguous suitable habitat in the southern United States and México, T. lecticularia has a diffuse suitable habitat distribution along both coasts of the same region, and T. sanguisuga has a disjoint suitable habitat distribution along the coasts of the United States. The ecological risk is highest in south Texas. 2. Incidence–based relative risk was computed at the county level using the Bayesian Besag–York–Mollié model and post–1960 T. cruzi incidence data. This risk is concentrated in south Texas. 3. The ecological and incidence–based risks were analyzed together in a multi–criteria dominance analysis of all counties and those counties in which there were as yet no reports of parasite incidence. Both analyses picked out counties in south Texas as those at highest risk. 4. As an alternative to the multi–criteria analysis, the ecological and incidence–based risks were compounded in a multiplicative composite risk model. Counties in south Texas emerged as those with the highest risk. 5. Risk as the relative expected exposure rate was computed using a multiplicative model for the composite risk and a scaled population county map for Texas. Counties with highest risk were those in south Texas and a few counties with high human populations in north, east, and central Texas showing that, though Chagas disease risk is concentrated in south Texas, it is not restricted to it.

Conclusions

For all of Texas, Chagas disease should be designated as reportable, as it is in Arizona and Massachusetts. At least for south Texas, lower than N, blood donor screening should be mandatory, and the serological profiles of human and canine populations should be established. It is also recommended that a joint initiative be undertaken by the United States and México to combat Chagas disease in the trans–border region. The methodology developed for this analysis can be easily exported to other geographical and disease contexts in which risk assessment is of potential value.     

Toxocariasis in North America: A Systematic Review

Toxocariasis is an important neglected tropical disease that can manifest as visceral or ocular larva migrans, or covert toxocariasis. All three forms pose a public health problem and cause significant morbidity in areas of high prevalence. To determine the burden of toxocariasis in North America, we conducted a systematic review of the literature following PRISMA guidelines. We found 18 articles with original prevalence, incidence, or case data for toxocariasis. Prevalence estimates ranged from 0.6% in a Canadian Inuit community to 30.8% in Mexican children with asthma. Commonly cited risk factors included: African-American race, poverty, male sex, and pet ownership or environmental contamination by animal feces. Increased prevalence of Toxocara spp. infection was linked in a group of case control studies conducted in Mexico to several high risk groups including waste pickers, asthmatic children, and inpatient psychiatry patients. Further research is needed to determine the true current burden of toxocariasis in North America; however the prevalence estimates gathered in this review suggest that the burden of disease is significant.     

Maternal serologic screening to prevent congenital toxoplasmosis: a decision-analytic economic model

Objective

To determine a cost-minimizing option for congenital toxoplasmosis in the United States.

Methodology/Principal Findings

A decision-analytic and cost-minimization model was constructed to compare monthly maternal serological screening, prenatal treatment, and post-natal follow-up and treatment according to the current French (Paris) protocol, versus no systematic screening or perinatal treatment. Costs are based on published estimates of lifetime societal costs of developmental disabilities and current diagnostic and treatment costs. Probabilities are based on published results and clinical practice in the United States and France. One- and two-way sensitivity analyses are used to evaluate robustness of results. Universal monthly maternal screening for congenital toxoplasmosis with follow-up and treatment, following the French protocol, is found to be cost-saving, with savings of $620 per child screened. Results are robust to changes in test costs, value of statistical life, seroprevalence in women of childbearing age, fetal loss due to amniocentesis, and to bivariate analysis of test costs and incidence of primary T. gondii infection in pregnancy. Given the parameters in this model and a maternal screening test cost of $12, screening is cost-saving for rates of congenital infection above 1 per 10,000 live births. If universal testing generates economies of scale in diagnostic tools—lowering test costs to about $2 per test—universal screening is cost-saving at rates of congenital infection well below the lowest reported rates in the United States of 1 per 10,000 live births.

Conclusion/Significance

Universal screening according to the French protocol is cost saving for the US population within broad parameters for costs and probabilities.     

Nonhuman primate models of intrauterine cytomegalovirus infection

Congenital human cytomegalovirus (HCMV) infection has long been recognized as a threat to the developing fetus, even though studies have shown that only a subset of congenital infections results in clinical signs of disease. Among the estimated 8000 children who develop sequelae from congenital CMV infection each year in the United States alone, most suffer permanent developmental defects within the central nervous system. Because there is currently no approved vaccine for HCMV, and anti-HCMV drugs are not administered to gravid women with congenital infection because of potential toxicity to the fetus, there is a clear clinical need for effective strategies that minimize infection in the mother, transplacental transmission of the virus, and/or fetal disease. Animal models provide a method to understand the mechanisms of HCMV persistence and pathogenesis, and allow for testing of novel strategies that limit prenatal infection and disease. The rhesus macaque model is especially well suited for these tasks because monkeys and humans share strong developmental, immunological, anatomical, and biochemical similarities due to their close phylogenetic relationship. This nonhuman primate model provides an invaluable system to accelerate the clinical development of promising new therapies for the treatment of human disease. This review addresses salient findings with the macaque model as they relate to HCMV infection and potential avenues of discovery, including studies of intrauterine CMV infection. The complexity of the natural history of HCMV is discussed, along with the ethical and logistical issues associated with studies during pregnancy, the recent contributions of animal research in this field of study, and future prospects for increasing our understanding of immunity against HCMV disease.     

The Neglected Arboviral Infections in Mainland China

The major arboviral diseases in mainland China include Japanese encephalitis, dengue fever, Crimean-Congo hemorrhagic fever (also known as Xinjiang hemorrhagic fever), and tick-borne encephalitis. These and other newly found arbovirus infections due to Banna virus and Tahyna virus contribute to a large and relatively neglected disease burden in China. Here we briefly review the literature regarding these arboviral infections in mainland China with emphasis on their epidemiology, primary vectors, phylogenetic associations, and the prevention programs associated with these agents in China.     

Congenital cytomegalovirus mortality in the United States, 1990-2006

Background

Congenital cytomegalovirus (CMV) infection is the most common intrauterine infection in the United States disproportionately affecting minority races and those of lower socio-economic class. Despite its importance there is little information on the burden of congenital CMV-related mortality in the US. To measure congenital CMV-associated mortality in the US and assess possible racial/ethnic disparities, we reviewed national death certificate data for a 17-year period.

Methods

Congenital CMV-associated deaths from 1990 through 2006 were identified from multiple-cause-coded death records and were combined with US census data to calculate mortality rates.

Results

A total of 777 congenital CMV-associated deaths occurred over the 17-year study period resulting in 56,355 years of age-adjusted years of potential life lost. 71.7% (557) of congenital CMV-associated deaths occurred in infants (age less than 1 year). Age-adjusted mortality rates stratified by race/ethnicity revealed mortality disparities. Age-adjusted rate ratios were calculated for each racial/ethnic group using whites as the reference. Native Americans and African Americans were 2.34 (95% CI, 2.11–2.59) and 1.89 (95% CI, 1.70–2.11) times respectively, more likely to die from congenital CMV than whites. Asians and Hispanics were 0.54 (95% CI, 0.44–0.66) and 0.96 (95% CI, 0.83–1.10) times respectively, less likely to die from congenital CMV than whites.

Conclusions/Significance

Congenital CMV infection causes appreciable mortality in the US exacting a particular burden among African Americans and Native Americans. Enhanced surveillance and increased screening are necessary to better understand the epidemiology of congenital CMV infection in addition to acceleration of vaccine development efforts.