John F. Modlin

Selenium Deficiency and Cardiomyopathy in Acquired Immunodeficiency Syndrome

Selenium deficiency is common in patients with human immunodeficiency virus infection and may contribute to the development of cardiomyopathy. A 5-year-old boy with congenital human immunodeficiency virus infection developed cardiomyopathy. Evaluation for reversible causes of cardiomyopathy was notable for the diagnosis of selenium deficiency. Cardiac function improved on selenium supplementation. The role of selenium in cardiac dysfunction and the need for nutritional evaluation and supplementation of malnourished patients with acquired immunodeficiency syndrome is discussed.

Expert Review on Poliovirus Immunity and Transmission

Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data.

Use of modified nucleotides and uracil-DNA glycosylase (UNG) for the control of contamination in the PCR-based amplification of RNA.

The inadvertent carryover of amplified fragments of nucleic acids (amplicons) is a potential source of contamination in the polymerase chain reaction. Recently, a method has been developed to generate amplicons with deoxyuracil triphosphate (dUTP) and to specifically hydrolyze these amplicons with uracil-DNA glycosylase (UNG) following the completion of the assay. We evaluated this system for the specific amplification of RNA from coxsackievirus A3 and B3. We found that RNA from both viruses could be amplified with dUTP, although the use of this triphosphate in place of TTP resulted in some loss of assay sensitivity. We also found that the dUTP-containing amplicons could be efficiently hydrolyzed by UNG, resulting in a 10,000,000-fold reduction in amplicon concentration with little effect on the native nucleic acid. The dUTP-UNG method has a great deal of potential for reducing amplicon contamination during the routine performance of nucleic acid amplification reactions.

Review and Assessment of Poliovirus Immunity and Transmission: Synthesis of Knowledge Gaps and Identification of Research Needs

With the intensifying global efforts to eradicate wild polioviruses, policymakers face complex decisions related to achieving eradication and managing posteradication risks. These decisions and the expanding use of inactivated poliovirus vaccine (IPV) trigger renewed interest in poliovirus immunity, particularly the role of mucosal immunity in the transmission of polioviruses. Sustained high population immunity to poliovirus transmission represents a key prerequisite to eradication, but poliovirus immunity and transmission remain poorly understood despite decades of studies. In April 2010, the U.S. Centers for Disease Control and Prevention convened an international group of experts on poliovirus immunology and virology to review the literature relevant for modeling poliovirus transmission, develop a consensus about related uncertainties, and identify research needs. This article synthesizes the quantitative assessments and research needs identified during the process. Limitations in the evidence from oral poliovirus vaccine (OPV) challenge studies and other relevant data led to differences in expert assessments, indicating the need for additional data, particularly in several priority areas for research: (1) the ability of IPV-induced immunity to prevent or reduce excretion and affect transmission, (2) the impact of waning immunity on the probability and extent of poliovirus excretion, (3) the relationship between the concentration of poliovirus excreted and infectiousness to others in different settings, and (4) the relative role of fecal-oral versus oropharyngeal transmission. This assessment of current knowledge supports the immediate conduct of additional studies to address the gaps.

Rationale for the sequential use of inactivated poliovirus vaccine and live attenuated poliovirus vaccine for routine poliomyelitis immunization in the United States

Despite the concerns mentioned in the last section, there are many reasons to believe that a polio immunization schedule that incorporates sequential doses of inactivated poliovirus vaccine and live attenuated poliovirus vaccine would provide both humoral and intestinal immunity to the fully immunized person that is at least as good, if not better, than the immunity achieved by the use of IPV or OPV alone. A substantial degree of protection should also extend to partially immunized and unimmunized preschool aged children in the community. Furthermore most of the cases of OPV-associated paralytic poliomyelitis could be prevented. Because the reasons for these beliefs are based on data from small studies and on inferences from related research, specific recommendations for a change from current polio immunization policy must depend on additional clinical research. Well-designed trials comparing several different options for sequencing both inactivated and live vaccines are needed, and these studies should focus carefully on both humoral and intestinal immunity conferred by the various vaccine schedules.

1047 RISK OF PERINATAL ECHOVIRUS INFECTION DURING A COMMUNITY OUTBREAK

During a community outbreak of enterovirus infection, 7 of 194 (3.6%) pregnant women were found to be excreting a prime strain of echovirus 11 at term. Each of the 7 virus positive women possessed serum neutralizing echovirus 11 antibody at delivery in titers ranging from 1:20 to 1:320, and the cord sera of the 7 infants born to these mothers also had antibody in titers of 1:10 to 1:640. The 7 infants of these women did not become ill, but 4 shed virus from the respiratory and/or gastrointestinal tract by three days of age. None of the infants of virus negative mothers cultured at hospital discharge (151 infants), or at two weeks of age (135 infants), became infected. In comparison, a previously reported group of 4 infants who died of generalized infection due to the same strain of echovirus 11 did not have detectable cord antibody.We conclude that passively acquired, transplacental antibody prevents severe, systemic echovirus disease, but does not prevent mucosal infection of the perinatally infected infant. Our experience also indicates that infants born to mothers who become infected with an enterovirus within the last week of pregnancy are at risk of serious perinatal disease.