National Center for Infectious Diseases

Flowery Branch, GA, United States

National Center for Infectious Diseases

Flowery Branch, GA, United States
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Lima-Junior J.C.,Institute Oswaldo Cruz | Banic D.M.,Institute Oswaldo Cruz | Tran T.M.,Emory University | Meyer V.S.E.,Emory University | And 8 more authors.
Vaccine | Year: 2010

Plasmodium vivax merozoite surface protein (PvMSP9) stimulates both cellular and humoral immune responses in individuals who are naturally infected by this parasite species. To identify immunodominant human T-cell epitopes in PvMSP9, we used the MHC class II binding peptide prediction algorithm ProPred. Eleven synthetic peptides representing predicted putative promiscuous T-cell epitopes were tested in IFN-γ and IL-4 ELISPOT assays using peripheral blood mononuclear cells (PBMC) derived from 142 individuals from Rondonia State, Brazil who had been naturally exposed to P. vivax infections. To determine whether the predicted epitopes are preferentially recognized in the context of multiple alleles, MHC Class II typing of the cohort was also performed. Five synthetic peptides elicited robust cellular responses, and the overall frequencies of IFN-γ and IL-4 responders to at least one of the promiscuous peptides were 62% and 46%, respectively. The frequencies of IFN-γ and IL-4 responders to each peptide were not associated with a particular HLA-DRB1 allelic group since most of the peptides induced a response in individuals of 12 out of 13 studied allelic groups. The prediction of promiscuous epitopes using ProPred led to the identification of immunodominant epitopes recognized by PBMC from a significant proportion of a genetically heterogeneous population exposed to malaria infections. The combination of several such T-cell epitopes in a vaccine construct may increase the frequency of responders and the overall efficacy of subunit vaccines in genetically distinct populations. © 2010 Elsevier Ltd. All rights reserved.

Lima-Junior J.C.,Institute Oswaldo Cruz | Jiang J.,Emory University | Rodrigues-da-Silva R.N.,Institute Oswaldo Cruz | Banic D.M.,Institute Oswaldo Cruz | And 9 more authors.
Vaccine | Year: 2011

The Plasmodium vivax Merozoite Surface Protein-3α (PvMSP-3α) is considered as a potential vaccine candidate. However, the detailed investigations of the type of immune responses induced in naturally exposed populations are necessary. Therefore, we aim to characterize the naturally induced antibody to PvMSP-3α in 282 individuals with different levels of exposure to malaria infections residents in Brazilian Amazon. PvMSP3 specific antibodies (IgA, IgG and IgG subclass) to five recombinant proteins and the epitope mapping by Spot-synthesis technique to full-protein sequence of amino acids (15aa sequence with overlapping sequence of 9aa) were performed. Our results indicates that PvMSP3 is highly immunogenic in naturally exposed populations, where 78% of studied individuals present IgG immune response against the full-length recombinant protein (PVMSP3-FL) and IgG subclass profile was similar to all five recombinant proteins studied with a high predominance of IgG1 and IgG3. We also observe that IgG and subclass levels against PvMSP3 are associated with malaria exposure. The PvMSP3 epitope mapping by Spot-synthesis shows a natural recognition of at least 15 antigenic determinants, located mainly in the two blocks of repeats, confirming the high immunogenicity of this region. In conclusion, PvMSP-3α is immunogenic in naturally exposed individuals to malaria infections and that antibodies to PvMSP3 are induced to several B cell epitopes. The presence of PvMSP3 cytophilic antibodies (IgG1 and IgG3), suggests that this mechanism could also occur in P. vivax. © 2011 Elsevier Ltd.

Brooks J.T.,National Center for Infectious Diseases | Brooks J.T.,Centers for Disease Control and Prevention | Degroot M.A.,Colorado State University | Beuchat L.R.,University of Georgia | And 2 more authors.
Foodborne Pathogens and Disease | Year: 2012

A 1998 investigation of an outbreak of Salmonella serotype Typhimurium infections among children tasting unpasteurized milk during tours of a dairy farm demonstrated a distribution of unusually long incubation periods (median, 8 days; interquartile range [IQR], 6-14 days). Bacterial isolates were highly acid tolerant and contained genes associated with protection against destructive phagocytic reactive oxygen intermediates. We hypothesize that exposure to low-dose oral inoculum of a pathogen with these properties could have contributed to cases of non-typhoidal salmonellosis with the longest incubation period reported to the Centers for Disease Control and Prevention (CDC). © 2012, Mary Ann Liebert, Inc.

Garcia H.H.,Cayetano Heredia Peruvian University | Gonzalez A.E.,National Major San Marcos University | Tsang V.C.W.,National Center for Infectious Diseases | Tsang V.C.W.,Centers for Disease Control and Prevention | And 12 more authors.
New England Journal of Medicine | Year: 2016

BACKGROUND: Taeniasis and cysticercosis are major causes of seizures and epilepsy. Infection by the causative parasite Taenia solium requires transmission between humans and pigs. The disease is considered to be eradicable, but data on attempts at regional elimination are lacking. We conducted a three-phase control program in Tumbes, Peru, to determine whether regional elimination would be feasible. METHODS: We systematically tested and compared elimination strategies to show the feasibility of interrupting the transmission of T. solium infection in a region of highly endemic disease in Peru. In phase 1, we assessed the effectiveness and feasibility of six intervention strategies that involved screening of humans and pigs, antiparasitic treatment, prevention education, and pig replacement in 42 villages. In phase 2, we compared mass treatment with mass screening (each either with or without vaccination of pigs) in 17 villages. In phase 3, we implemented the final strategy of mass treatment of humans along with the mass treatment and vaccination of pigs in the entire rural region of Tumbes (107 villages comprising 81,170 people and 55,638 pigs). The effect of the intervention was measured after phases 2 and 3 with the use of detailed necropsy to detect pigs with live, nondegenerated cysts capable of causing new infection. The necropsy sampling was weighted in that we preferentially included more samples from seropositive pigs than from seronegative pigs. RESULTS: Only two of the strategies implemented in phase 1 resulted in limited control over the transmission of T. solium infection, which highlighted the need to intensify the subsequent strategies. After the strategies in phase 2 were implemented, no cyst that was capable of further transmission of T. solium infection was found among 658 sampled pigs. One year later, without further intervention, 7 of 310 sampled pigs had live, nondegenerated cysts, but no infected pig was found in 11 of 17 villages, including all the villages in which mass antiparasitic treatment plus vaccination was implemented. After the final strategy was implemented in phase 3, a total of 3 of 342 pigs had live, nondegenerated cysts, but no infected pig was found in 105 of 107 villages. CONCLUSIONS: We showed that the transmission of T. solium infection was interrupted on a regional scale in a highly endemic region in Peru. Copyright © 2016 Massachusetts Medical Society.

Gavidia C.M.,National Major San Marcos University | Verastegui M.R.,Cayetano Heredia Peruvian University | Garcia H.H.,Cayetano Heredia Peruvian University | Lopez-Urbina T.,National Major San Marcos University | And 11 more authors.
PLoS Neglected Tropical Diseases | Year: 2013

Background:Serological tests have been used for the diagnosis of Taenia solium infection in pigs. However, those serological results do not necessarily correlate with the actual infection burden after performing pig necropsy. This study aimed to evaluate the Electro Immuno Transfer Blot (EITB) seropositivity with infection burden in naturally infected pigs.Methodology/Principal Findings:In an endemic area of Peru, 476 pigs were sampled. Seroprevalence was 60.5±4.5% with a statistically higher proportion of positive older pigs (>8 months) than young pigs. The logistic model showed that pigs >8 month of age were 2.5 times more likely to be EITB-positive than ≤8 months. A subset of 84 seropositive pigs were necropsied, with 45.2% (38/84) positive to 1-2 bands, 46.4% (39/84) to 3 bands, and 8.3% (7/84) to 4+ bands. 41 out of 84 positive pigs were negative to necropsy (48.8%) and 43 (51%) had one or more cysts (positive predictive value). Older pigs showed more moderate and heavy infection burdens compared to younger pigs. In general, regardless of the age of the pig, the probability of having more cysts (parasite burden) increases proportionally with the number of EITB bands.Conclusions/Significance:The probability of being necropsy-positive increased with the number of bands, and age. Therefore, the EITB is a measure of exposure rather than a test to determine the real prevalence of cysticercosis infection. © 2013 Gavidia et al.

Lima-Junior J.C.,Instituto Oswaldo Cruz | Lima-Junior J.C.,Oswaldo Cruz Foundation | Rodrigues-da-Silva R.N.,Oswaldo Cruz Foundation | Banic D.M.,Instituto Oswaldo Cruz | And 11 more authors.
PLoS ONE | Year: 2012

Background: The antibody response generated during malaria infections is of particular interest, since the production of specific IgG antibodies is required for acquisition of clinical immunity. However, variations in antibody responses could result from genetic polymorphism of the HLA class II genes. Given the increasing focus on the development of subunit vaccines, studies of the influence of class II alleles on the immune response in ethnically diverse populations is important, prior to the implementation of vaccine trials. Methods and Findings: In this study, we evaluated the influence of HLA-DRB1* and -DQB1* allelic groups on the naturally acquired humoral response from Brazilian Amazon individuals (n = 276) against P. vivax Merozoite Surface Protein-1 (MSP-1), MSP-3α and MSP-9 recombinant proteins. Our results provide information concerning these three P. vivax antigens, relevant for their role as immunogenic surface proteins and vaccine candidates. Firstly, the studied population was heterogeneous presenting 13 HLA-DRB1* and 5 DQB1* allelic groups with a higher frequency of HLA-DRB1*04 and HLA-DQB1*03. The proteins studied were broadly immunogenic in a naturally exposed population with high frequency of IgG antibodies against PvMSP1-19 (86.7%), PvMSP-3 (77%) and PvMSP-9 (76%). Moreover, HLA-DRB1*04 and HLA-DQB1*03 alleles were associated with a higher frequency of IgG immune responses against five out of nine antigens tested, while HLA-DRB1*01 was associated with a high frequency of non-responders to repetitive regions of PvMSP-9, and the DRB1*16 allelic group with the low frequency of responders to PvMSP3 full length recombinant protein. Conclusions: HLA-DRB1*04 alleles were associated with high frequency of antibody responses to five out of nine recombinant proteins tested in Rondonia State, Brazil. These features could increase the success rate of future clinical trials based on these vaccine candidates. © 2012 Lima-Junior et al.

Malisa A.L.,Sokoine University of Agriculture | Malisa A.L.,Ifakara Health Institute IHI | Pearce R.J.,London School of Hygiene and Tropical Medicine | Abdulla S.,Ifakara Health Institute IHI | And 4 more authors.
Malaria Journal | Year: 2010

Background. It is argued that, the efficacy of anti-malarials could be prolonged through policy-mediated reductions in drug pressure, but gathering evidence of the relationship between policy, treatment practice, drug pressure and the evolution of resistance in the field is challenging. Mathematical models indicate that drug coverage is the primary determinant of drug pressure and the driving force behind the evolution of drug resistance. These models show that where the basis of resistance is multigenic, the effects of selection can be moderated by high recombination rates, which disrupt the associations between co-selected resistance genes. Methods. To test these predictions, dhfr and dhps frequency changes were measured during 2000-2001 while SP was the second-line treatment and contrasted these with changes during 2001-2002 when SP was used for first-line therapy. Annual cross sectional community surveys carried out before, during and after the policy switch in 2001 were used to collect samples. Genetic analysis of SP resistance genes was carried out on 4,950 Plasmodium falciparum infections and the selection pressure under the two policies compared. Results. The influence of policy on the parasite reservoir was profound. The frequency of dhfr and dhps resistance alleles did not change significantly while SP was the recommended second-line treatment, but highly significant changes occurred during the subsequent year after the switch to first line SP. The frequency of the triple mutant dhfr (N51I,C59R,S108N) allele (conferring pyrimethamine resistance) increased by 37% - 63% and the frequency of the double A437G, K540E mutant dhps allele (conferring sulphadoxine resistance) increased 200%-300%. A strong association between these unlinked alleles also emerged, confirming that they are co-selected by SP. Conclusion. The national policy change brought about a shift in treatment practice and the resulting increase in coverage had a substantial impact on drug pressure. The selection applied by first-line use is strong enough to overcome recombination pressure and create significant linkage disequilibrium between the unlinked genetic determinants of pyrimethamine and sulphadoxine resistance, showing that recombination is no barrier to the emergence of resistance to combination treatments when they are used as the first-line malaria therapy. © 2010 Malisa et al; licensee BioMed Central Ltd.

Malisa A.L.,Sokoine University of Agriculture | Malisa A.L.,Ifakara Health Institute IHI | Pearce R.J.,London School of Hygiene and Tropical Medicine | Mutayoba B.M.,Sokoine University of Agriculture | And 5 more authors.
Malaria Journal | Year: 2011

Background: Sulphadoxine-pyrimethamine (SP) resistance is now widespread throughout east and southern Africa and artemisinin compounds in combination with synthetic drugs (ACT) are recommended as replacement treatments by the World Health Organization (WHO). As well as high cure rates, ACT has been shown to slow the development of resistance to the partner drug in areas of low to moderate transmission. This study looked for evidence of protection of the partner drug in a high transmission African context. The evaluation was part of large combination therapy pilot implementation programme in Tanzania, the Interdisciplinary Monitoring Programme for Antimalarial Combination Therapy (IMPACT-TZ). Methods. The growth of resistant dhfr in a parasite population where SP Monotherapy was the first-line treatment was measured for four years (2002-2006), and compared with the development of resistant dhfr in a neighbouring population where SP + artesunate (SP+AS) was used as the first-line treatment during the same interval. The effect of the differing treatment regimes on the emergence of resistance was addressed in three ways. First, by looking at the rate of increase in frequency of pre-existing mutant dhfr alleles under monotherapy and combination therapy. Second, by examining whether de-novo mutant alleles emerged under either treatment. Finally, by measuring diversity at three dhfr flanking microsatellite loci upstream of the dhfr gene. Results: The reduction in SP selection pressure resulting from the adoption of ACT slowed the rate of increase in the frequency of the triple mutant resistant dhfr allele. Comparing between the two populations, the higher levels of genetic diversity in sequence flanking the dhfr triple mutant allele in the population where the ACT regimen had been used indicates the reduction in SP selection pressure arising from combination therapy. Conclusion: The study demonstrated that, alleles containing two mutations at the dhfr have arisen at least four times independently while those containing triple mutant dhfr arose only once, and were found carrying a single unique Asian-type flanking sequence, which apparently drives the spread of pyrimethamine resistance associated dhfr alleles in east Africa. SP+AS is not recommended for use in areas where SP cure rates are less than 80% but this study reports an observed principle of combination protection from an area where pyrimethamine resistance was already high. © 2011Malisa et al; licensee BioMed Central Ltd.

PubMed | World Health Organization, Working in Tandem Ltd, Russian Academy of Medical Sciences, Serum Institute of India and 5 more.
Type: Congresses | Journal: Vaccine | Year: 2015

On 5-7 May 2014, the World Health Organization (WHO) convened the second integrated meeting on influenza vaccines that induce broadly protective and long-lasting immune responses. Around 100 invited experts from academia, the vaccine industry, research and development funders, and regulatory and public health agencies attended the meeting. Areas covered included mechanisms of protection in natural influenza-virus infection and vaccine-induced immunity, new approaches to influenza-vaccine design and production, and novel routes of vaccine administration. A timely focus was on how this knowledge could be applied to both seasonal influenza and emerging viruses with pandemic potential such as influenza A (H7N9), currently circulating in China. Special attention was given to the development of possible universal influenza vaccines, given that the Global Vaccine Action Plan calls for at least one licensed universal influenza vaccine by 2020. This report highlights some of the topics discussed and provides an update on studies published since the report of the previous meeting.

Kostoff R.N.,Mitre Corporation | Morse S.A.,National Center for Infectious Diseases
Scientometrics | Year: 2011

Text mining was used to extract technical intelligence from the open source global SARS research literature. A SARS-focused query was applied to the Science Citation Index (SCI) (SCI 2008) database for the period 1998-early 2008. The SARS research literature infrastructure (prolific authors, key journals/institutions/countries, most cited authors/journals/documents) was obtained using bibliometrics, and the SARS research literature technical structure (hierarchical taxonomy) was obtained using computational linguistics/document clustering. © 2010 Akadémiai Kiadó, Budapest, Hungary.

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