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MaHPIC Public Data Releases

All results are a product of the MaHPIC.  Curation and maintenance of all data and metadata are the responsibility of the MaHPIC:  Mary Galinski mgalins@emory.edu (MaHPIC Program Director), Jessica Kissinger jkissing@uga.edu (MaHPIC Co-Program Director), and Alberto Moreno camoren@emory.edu (MaHPIC Co-Program Director).

For questions about MaHPIC Public Data Releases contact mahpic@emory.edu. 

The MaHPIC is dedicated to the release of project results to promote discoverability, reuse, and the generation of novel hypotheses.  Experiment results are released concomitant with project publications in a timely manner according to contract requirements.  Results from each experiment and data type are released to appropriate public repositories.  MaHPIC is partnered with the PlasmoDB database, a project of the Eukaryotic Pathogen Database Project (EuPathDB), developed, in part, by Jessica Kissinger of the MaHPIC for the release of data to the public.  
A description of MaHPIC experiments with publicly released data, and links to datasets organized by data type are below.  Additional experiments and datasets will be added as they are released. 
 MaHPIC Reference Genomes

Experiment 01

Title: Macaca mutatta infected with Plasmodium coatneyi Hackeri strain infected red blood cells

Description: Be aware that though this dataset is included in the body of MaHPIC results, it was produced before the MaHPIC project started. As of this writing, only the clinical results are planned for public release. Also, different from most MaHPIC datasets, there are no clinical timepoints included in the results. Before the experimental infection, the macaques received an intravenous infusion of a water-soluble biotin derivative to determine the erythrocyte lifespan via daily quantification of the biotinylated cells using flow cytometry. Clinical, hematological, parasitological, and metabolomics measures were collected in the course of the infection. Within the MaHPIC, this project is known as 'Experiment 01'. This dataset was produced by Dr. Alberto Moreno and Monica Cabrera-Mora at Emory University. To access other publicly available data from MaHPIC Experiments visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: 

Experiment 02

Title: Uninfected Macaca mulatta that serve as a control for in vivo biotinylation studies

Description: Be aware that though this dataset is included in the body of MaHPIC results, it was produced before the MaHPIC project started. As of this writing, only the clinical results are planned for public release. Also, different from most MaHPIC datasets, there are no clinical timepoints included in the results. The macaques received an intravenous infusion of a water-soluble biotin derivative to determine the erythrocyte lifespan via daily quantification of the biotinylated cells using flow cytometry. Clinical, hematological, and metabolomics measures were collected in the course of the follow-up. Within the MaHPIC, this project is known as 'Experiment 02'. This dataset was produced by Dr. Alberto Moreno Emory University. To access other publicly available data from MaHPIC Experiments visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: 

Experiment 03

Title: Macaca mulatta infected with Plasmodium coatneyi Hackeri strain to produce and integrate clinical, hematological, parasitological, and omics measures of acute, recrudescent, and chronic infections.

Description: Malaria-naive male rhesus macaques (Macaca mulatta), approximately four years of age, were inoculated intravenously with salivary gland sporozoites produced and isolated at the Centers for Disease Control and Prevention from multiple Anopheles species (An. dirus, An. gambiae, and An. stephensi) and then profiled for clinical, hematological, parasitological, immunological, functional genomic, lipidomic, proteomic, and metabolomic measurements. The experiment was designed for 100 days, and pre- and post-100 day periods to prepare subjects and administer curative treatments respectively. The anti-malarial drug artemether was subcuratively administered to all subjects at the initial peak of infection, one out of the five macaques received four additional subcurative treatments for subsequent recrudescence peaks.  The experimental infection in one subject was ineffective but the macaque was followed-up for the same period of 100 days. The different clinical phases of the infection were clinically determined for each subject.  Blood-stage curative doses of artemether were administered to all subjects at the end of the study.  Capillary blood samples were collected daily for the measurement of CBCs, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood and bone marrow samples were collected at seven time points for functional genomic, proteomic, lipidomic, and immunological analyses. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: 

Experiment 04

Title: Macaca mulatta infected with Plasmodium cynomolgi B strain to produce and integrate clinical, hematological, parasitological, and omics measures of acute primary infection and relapses.

 

Description: Malaria-naive male rhesus macaques (Macaca mulatta), approximately three years of age, were inoculated intravenously with salivary gland sporozoites produced and isolated at the Centers for Disease Control and Prevention from multiple Anopheles species (An. dirus, An. gambiae, and An. stephensi) and then profiled for clinical, hematological, parasitological, immunological, functional genomic, lipidomic, proteomic, and metabolomic measurements. The experiment was designed for 100 days, and pre- and post-100 day periods to prepare subjects and administer curative treatments respectively. The anti-malarial drug artemether was subcuratively administered selectively to several subjects during the primary parasitemia to suppress clinical complications and to all animals for curative treatment of blood-stage infections to allow detection of relapses. One subject was euthanized during the 100-day experimental period due to clinical complications. The anti-malarial drugs primaquine and chloroquine were administered to all remaining subjects at the end of the study for curative treatment of the liver and blood-stage infections, respectively. Capillary blood samples were collected daily for the measurement of CBCs, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood and bone marrow samples were collected at seven time points for functional genomic, proteomic, lipidomic, and immunological analyses. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: 

 

Experiment 04R

Title: E04R - Experiment 04 Functional Genomics Resequencing-Macaca mulatta infected with Plasmodium cynomolgi B strain to produce clinical and omics measures of infection and relapse.

 

Description:  Malaria-naive male rhesus macaques (Macaca mulatta), approximately three years of age, were inoculated intravenously with salivary gland sporozoites produced and isolated at the Centers for Disease Control and Prevention fom multiple Anopheles species (An. dirus, An. gambiae, and An. stephensi) and then profiled for clinical, hematological, parasitological, immunological, functional genomic, lipidomic, proteomic, and metabolomic measurements.  The experiment was designed for 100 days, and pre- and post-100 day periods to prepare subjects and administer curative treatments respectively.  The anti-malarial drug artemether was subcuratively administered selectively to several subjects during the primary parasitemia to suppress clinical complications and to all animals for curative treatment of blood-stage infections to allow detection of relapses.  One subject was euthanized during the 100-day experimental period due to clinical complications.  The anti-malarial drugs primaquine and chloroquine were administered to all remaining subjects at the end of the study for curative treatment of the liver and blood-stage infections, respectively.  Capillary blood samples were collected daily for the measurement of CBCs, reticulocytes, and parasitemias.  Capillary blood samples were collected every other dayto obtain plasma for metabolomic analysis.  Venous blood and bone marrow samples were collected at seven time points for functional genomic, proteomic, lipidomic, and immunological analyses.  Within the MaHPIC, this project is known as 'Experiment 04R'.  This dataset was produced by Yerkes Genomics Core.  To access other publicly available results from E04R and other MaHPIC Experiments, including clinical results (specifics on drugs administered, diet, and veterinary interventions), and other omics, visit http://plasmodb.org/plasmo/mahpic.jsp.  This page will be upated as datasets are released to the public.  E04R is a 'resequencing' of the same samples from E04.  Resequencing for E04R was processed with SOPs and technology consistent with that used for E23R, E24, and E25 so that results from these experiments could be reliably compared.  E04R does not replace E04, these are distinct datasets.  Relative to e04, E04R is only for MaHPIC Yerkes Sequencing and Functional Genomics results.  Only E04R is intended for comparison with E23R, E24, and E25.  The experimental design and protocols for this study were approved by the Emor University Institutional Animal Care and Use Committee (IACUC).

Available Datasets:

Experiment 06

 

Title: Macaca mulatta infected with Plasmodium knowlesi to produce and integrate clinical, hematological, parasitological, omics, telemetric, and histopathological measures of acute primary infection.

Description: Telemetry devices (DSI, model L11) with blood pressure sensors and ECG leads were surgically implanted in four malaria-naive male rhesus macaques (Macaca mulatta), approximately five years of age. After a resting period of two weeks, physiological data that include activity, temperature, ECG, and blood pressure were continuously collected. Two weeks after activation of the telemetry implant, the macaques were inoculated intravenously with cryopreserved salivary gland sporozoites. The cryopreserved batch of P. knowlesi sporozoites were produced, isolated and cryopreserved at the Centers for Disease Control and Prevention from Anopheles dirus. After experimental infection, the infected macaques were profiled for clinical, hematological, parasitological, immunological, functional genomic, proteomic, and metabolomic measurements. The experiment was designed for terminal necropsies scheduled at the log phase of the infection or at the peak of parasitemias. Capillary blood samples were collected daily for the measurement of CBCs, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood and bone marrow samples were collected at five time points for functional genomic, targeted proteomic, targeted metabolomics, and immunological analyses. Physiological data were continuously captured via telemetry. Within the MaHPIC, this project is known as 'Experiment 06'. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC) and the MRMC Office of Research Protection Animal Care and Use Review Office (ACURO). 

Available Datasets:

Experiment 07

 

Title: Macaca fascicularis infected with Plasmodium knowlesi A strain to produce and integrate clinical, hematological, parasitological, omics, telemetric and histopathological measures of acute primary infection.

Description: E07 was originally planned to use 'fresh' non-cryo preserved P. knowlesi sporozoites for inoculation. Inoculation with fresh sporozoites took place on 11/01/16 and did not result in a successful infection. Consequently, there was a second inoculation using cryopreserved sporozoites performed on 1/20/17. Hence there was a decision to divide E07 into 'E07A' (containing samples and results from the failed inoculation) and 'E07B' (containing samples and results from the successful inoculation with cryopreserved sporozoites on 1/20/17). Telemetry devices (DSI, model L11) with blood pressure sensors and ECG leads were surgically implanted in seven malaria-naive male long-tailed macaques (Macaca fascicularis), approximately five years of age. After a resting period, the telemetry implants were turned on and physiological data that include activity, temperature, ECG, and blood pressure were continuously collected. After failed inoculation with a fresh preparation of salivary gland sporozoites in E07A, implants were deactivated to preserve battery life. Between E07A and E07B, a single Rhesus macaque (M. mulatta) was added to the cohort as an infection control with no telemetry implant. At the start of E07B, telemetry implants were reactivated. Ten days after reactivation all animals were inoculated intravenously with cryopreserved salivary gland sporozoites. The cryopreserved batch of P. knowlesi sporozoites was produced, isolated and cryopreserved at the Centers for Disease Control and Prevention from Anopheles dirus. After experimental infection, the infected macaques were profiled for clinical, hematological, parasitological, immunological, functional genomic, proteomic, and metabolomic measurements. The experiment was designed for terminal necropsies scheduled at the log phase of the infection, at the peak of parasitemias, at the middle of the chronic phase, or at the end of the follow-up period 45 days after experimental infection. Capillary blood samples were collected daily for the measurement of CBCs, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood and bone marrow samples were collected at six time points for functional genomic, targeted proteomic, targeted metabolomics, and immunological analyses. Physiological data were continuously captured via telemetry. Within the MaHPIC, this project is known as 'Experiment 07'. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC) and the MRMC Office of Research Protection Animal Care and Use Review Office (ACURO). 

Available Datasets:

 

Experiment 13

Title: Uninfected Macaca mulatta exposed to pyrimethamine to produce and integrate clinical, hematological, and omics control measures.

 

Description: Uninfected, malaria-naive, male rhesus macaques (Macaca mulatta), approximately two years of age, were inoculated intravenously with a preparation of salivary gland material derived from non-infected Anopheles dirus and profiled for clinical, hematological, functional genomic, lipidomic, proteomic, and metabolomic measurements. Samples were generated and analyzed to investigate the effects of the pharmacological intervention with the anti-malarial drug pyrimethamine on normal individuals. The experiment was designed for 100 days plus a follow-up period, with pyrimethamine administered at three different time points to coincide with the predicted treatment days of experimentally infected rhesus macaques. Capillary blood samples were collected daily for the measurement of CBCs and reticulocytes. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood samples and bone marrow aspirates were collected at seven time points before and after three rounds of drug administration for functional genomic, proteomic, and lipidomic analyses. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: 

Experiment 15
Title: Aotus nancymaae infected with P. vivax Brazil VII to produce clinical and omics measures of primary infections and relapses.
Description: Malaria-naive Aotus nancymaae were inoculated intravenously with salivary gland sporozoites produced and isolated at the Centers for Disease Control and Prevention from multiple Anopheles species (An. gambiae, An. stephensi, and An. freeborni) then profiled for clinical, hematological, parasitological, immunological, functional genomic, and metabolomic measurements. The experiment was performed for 121 days. The first inoculation attempt was virtually unsuccessful as only one of seven animals developed blood-stage infection. This animal was treated for the blood-stage infection.  All animals were re-challenged approximately one month later. Upon re-challenge all animals developed blood-stage infections with similar parasitological kinetics. After infections became chronic, the anti-malarial drug artemether was administered to curatively treat blood-stage infections. No sub-curative treatments were administered during this study because none of the animals developed severe disease. At the end of the study, the anti-malarial drugs primaquine and chloroquine were administered to all animals for curative treatment of the liver and blood-stage infections, respectively. Venous blood samples were collected only on clinically determined ‘timepoint’ days for the measurement of CBCs, reticulocytes, parasitemias, and downstream omics and immunological analyses. Small sample volumes were collected daily or every other day for the measurement of parasitemia. Within the MaHPIC, this project is known as ‘Experiment 15’.  The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC). 
Available Datasets:
Experiment 18

 

Title: Uninfected Macaca mulatta exposed to artemether to produce and integrate clinical, hematological, and omics control measures.


Description: An uninfected, malaria-naive, male rhesus macaque (Macaca mulatta), approximately two years of age, was inoculated intravenously with a preparation of salivary gland material derived from non-infected Anopheles dirus and profiled for clinical, hematological, functional genomic, and proteomic measurements. Samples were generated and analyzed to investigate the effects of the pharmacological intervention with the anti-malarial drug artemether on normal individuals. The experiment was designed for 100 days, with artemether administered at three different time points to coincide with the predicted subcurative or curative treatment days of experimentally infected rhesus macaques. Capillary blood samples were collected daily for the measurement of CBCs and reticulocytes. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood samples and bone marrow aspirates were collected at seven-time points before and after three rounds of drug administration for functional genomic and proteomic analyses.  The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets:

Experiment 20

Title: Macaca mulatta previously infected with Plasmodium coatneyi Hackeri strain infected red blood cells exposed to a homologous re-challenge 11 months after the first infection (Experiment 01).

 

Description: Be aware that though this dataset is included in the body of MaHPIC results, it was produced before the MaHPIC project started. As of this writing, only the clinical results are planned for public release. Also, different from most MaHPIC datasets, there are no clinical timepoints included in the results. Before the experimental infection, the macaques received an intravenous infusion of a water-soluble biotin derivative to determine the erythrocyte lifespan via daily quantification of the biotinylated cells using flow cytometry. Clinical, hematological, parasitological, and metabolomics measures were collected in the course of the infection. Within the MaHPIC, this project is known as 'Experiment 20'. This dataset was produced by Dr. Alberto Moreno at Emory University. To access other publicly available data from MaHPIC Experiments visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: 

Experiment 21
Title: Uninfected Macaca mulatta that serve as a control for in vivo biotinylation studies ten months after the first infusion (Experiment 02)

Description: Be aware that though this dataset is included in the body of MaHPIC results, it was produced before the MaHPIC project started. As of this writing, only the clinical results are planned for public release. Also, different from most MaHPIC datasets, there are no clinical timepoints included in the results. The macaques received a second intravenous infusion of a water-soluble biotin derivative ten months after the first infusion (E02) to determine the erythrocyte lifespan via daily quantification of the biotinylated cells using flow cytometry. Clinical, hematological, and metabolomics measures were collected in the course of the follow-up. Within the MaHPIC, this project is known as 'Experiment 21'. This dataset was produced by Dr. Alberto Moreno at Emory University. To access other publicly available data from MaHPIC Experiments visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: 

Experiment 23

Title: Macaca mulatta infected with Plasmodium cynomolgi B strain to produce and integrate clinical, hematological, parasitological, and omics measures of acute primary infection and relapses.

Description: Malaria-naive male rhesus macaques (Macaca mulatta), approximately four years of age, were inoculated intravenously with salivary gland sporozoites produced and isolated at the Centers for Disease Control and Prevention from multiple Anopheles species (An. dirus, An. gambiae, and An. stephensi) and then profiled for clinical, hematological, parasitological, immunological, functional genomic, lipidomic, proteomic, and metabolomic measurements. The experiment was designed for about 100 days, with pre- and post-100 day periods to prepare subjects and administer curative treatments respectively. During the 100-day period subjects experienced periods of patent and sub-patent infection. The anti-malarial drug artemether was subcuratively administered to subjects after the initial peak of infection, if subjects were not able to self-resolve.  Blood-stage curative artemether was administered to all subjects following peak infection, and following a period of relapse infection.  All peaks were clinically determined for each subject.  The anti-malarial drugs primaquine and chloroquine were administered to all subjects at the end of the study for curative treatment of the liver and blood-stage infections, respectively.  Capillary blood samples were collected daily for the measurement of CBCs, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood and bone marrow samples were collected at seven time points for functional genomic, proteomic, lipidomic, and immunological analyses. This is an iteration of Experiment 04 with the same parasite-host combination and sampling and treatment adjustments made, and this is the first in a series of experiments that includes subsequent homologous (Experiment 24, P. cynomolgi B strain) and heterologous (Experiment 25, P. cynomolgi strain ceylonensis) challenges of individuals from the Experiment 23 cohort.  One subject was not included in subsequent experiments due to persistent behavioral issues that prevented sample collection. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: 

 

Experiment 23R

 

Title: Functional Genomics Resequencing - Macaca mulatta infected with Plasmodium cynomolgi B strain to produce and integrate clinical, hematological, parasitological, and omics measures of acute primary infection and relapses.

Description: Malaria-naive male rhesus macaques (Macaca mulatta), approximately four years of age, were inoculated intravenously with salivary gland sporozoites produced and isolated at the Centers for Disease Control and Prevention from multiple Anopheles species (An. dirus, An. gambiae, and An. stephensi) and then profiled for clinical, hematological, parasitological, immunological, functional genomic, lipidomic, proteomic, and metabolomic measurements. The experiment was designed for about 100 days, with pre- and post-100 day periods to prepare subjects and administer curative treatments respectively. During the 100-day period subjects experienced periods of patent and sub-patent infection. The anti-malarial drug artemether was subcuratively administered to subjects after the initial peak of infection, if subjects were not able to self-resolve.  Blood-stage curative artemether was administered to all subjects following peak infection, and following a period of relapse infection.  All peaks were clinically determined for each subject.  The anti-malarial drugs primaquine and chloroquine were administered to all subjects at the end of the study for curative treatment of the liver and blood-stage infections, respectively.  Capillary blood samples were collected daily for the measurement of CBCs, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood and bone marrow samples were collected at seven time points for functional genomic, proteomic, lipidomic, and immunological analyses.  E23 is an iteration of Experiment 04 with the same parasite-host combination. E23 is the first in a series of experiments that includes subsequent homologous (Experiment 24, P. cynomolgi B strain) and heterologous (Experiment 25, P. cynomolgi strain ceylonensis) challenges of individuals from the E23 cohort.  Note that one E23 subject was not included in subsequent experiments due to persistent behavioral issues that prevented sample collection.  Within the MaHPIC, this project is known as ‘Experiment 23R’.  E23R is a 'resequencing' of all samples from E23, processed with SOPs and technology consistent with that used for E04R, E24, and E25 so that results from these experiments could be reliably compared.  Only E23R is intended for comparison with E04R, E24, and E25.  The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets
     Functional Genomics - Available at NCBI's GEO

Experiment 24

Title: Macaca mulatta infected with Plasmodium cynomolgi B strain, in a homologous challenge, to produce and integrate clinical, hematological, parasitological, and omics measures of acute primary infection and relapses.

 

Description: Male rhesus macaques (Macaca mulatta), cleared of previous infection with  P. cynomolgi B strain via treatment with the anti-malarial drugs artemether, chloroquine, and primaquine,  approximately five years of age, were inoculated intravenously with salivary gland sporozoites produced and isolated at the Centers for Disease Control and Prevention from multiple Anopheles species (An. dirus, An. gambiae, and An. stephensi) and then profiled for clinical, hematological, parasitological, immunological, functional genomic, lipidomic, and metabolomic measurements. The experiment included 1 pre-inoculation day, 35 experiment days, and 10 post-experiment days.  The anti-malarial drugs primaquine and chloroquine were administered to all subjects at the end of the study for curative treatment of the liver and blood-stage infections, respectively.  Capillary blood samples were collected daily for the measurement of CBCs, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood samples were collected at three time points for functional genomic, lipidomic, and immunological analyses. This is the second in a series of experiments that includes infection of malaria-naïve subjects (Experiment 23, P. cynomolgi B strain) and heterologous challenge (Experiment 25, P. cynomolgi strain ceylonensis) for the individuals from the same cohort. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: 

Experiment 25

Title: Macaca mulatta infected with Plasmodium cynomolgi strain ceylonensis, in a heterologous challenge, to produce and integrate clinical, hematological, parasitological, and omics measures of acute primary infection and relapses

 

Description: Male rhesus macaques (Macaca mulatta), cleared of previous infection with  P. cynomolgi B strain via treatment with the anti-malarial drugs artemether, chloroquine, and primaquine,  approximately five years of age, were inoculated intravenously with salivary gland sporozoites produced and isolated at the Centers for Disease Control and Prevention from multiple Anopheles species (An. dirus, An. gambiae, and An. stephensi) and then profiled for clinical, hematological, parasitological, immunological, functional genomic, lipidomic, proteomic, and metabolomic measurements. The experiment included 8 pre-inoculation days, 49 experiment days, and 4 post-experiment days.  The anti-malarial drug artemether was subcuratively administered to subjects at the initial peak of infection, if subjects were not able to self-resolve their parasitemias.  Peak infection was determined clinically for each subject.  The anti-malarial drugs primaquine and chloroquine were administered to all subjects at the end of the study for curative treatment of the liver and blood-stage infections, respectively.  Capillary blood samples were collected daily for the measurement of CBCs, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood samples were collected at five time points for functional genomic, lipidomic, proteomic, and immunological analyses. This is the third and final of a series of experiments that includes infection of malaria-naïve subjects (Experiment 23, P. cynomolgi B strain) and homologous challenge (Experiment 24, P. cynomolgi B strain) of individuals from the same cohort. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: 

 

Experiment 30

Title: Experiment 30: Pilot experiment for Macaca mulatta infected with Plasmodium knowlesi Malayan strain sporozoites to produce and integrate clinical, hematological, parasitological, omics, telemetric and histopathologicalmeasures of acute primary infection. 

 

Description:  Telemetry devices (DSI, model L11) with blood pressure sensors and electrocardiogram (ECG) leads were surgically implanted in two malaria-naive male rhesus macaques (Macaca mulatta), approximately three years of age.  After a resting period of two weeks, physiological data that include activity, temperature, ECG, and blood pressure were continuously collected.  Two weeks after activation of the telemetry implant, the macaques were inoculated intravenously with cryopreserved P. knowlesi Malayan strain salivary gland sporozoites, obtained from Anopheles dirusinfected with parasites from the Pk1A+ clone. The P. knowlesi sporozoites were produced, isolated and cryopreserved at the Centers for Disease Control and Prevention.  After inoculation, the macaques were profiled for clinical, hematological, parasitological, immunological, functional genomic, lipidomic, proteomic, metabolomic, telemetric and histopathological measurements. The experiment was designed for pathology studies, with terminal necropsies on days 11 (RKy15) or 19 (Red16).  The anti-malarial drug artemether was subcuratively administered selectively to one subject (REd16) during the primary parasitemia to suppress clinical complications. Capillary blood samples were collected daily for the measurement of complete blood counts, reticulocytes, and parasitemias. Capillary blood samples were collected every other day to obtain plasma for metabolomic analysis. Venous blood and bone marrow samples were collected at five timepoints for functional genomic, proteomic, lipidomic, and immunological analyses. Physiological data were continuously captured via telemetry.  Within the MaHPIC, this project is known as ‘Experiment 30’.   The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC) and the MRMC Office of Research Protection Animal Care and Use Review Office (ACURO).

Available Datasets:

Experiment 33

Title: Mixed cohort of Macaca mulatta and Macaca fascicularis infected with Plasmodium knowlesi Malayan strain sporozoites to produce and integrate clinical, hematological, parasitological, omics, and histopathological measures of acute primary infection.

 

Description: A mixed cohort of six malaria-naive male Macaca mulatta (n=2) and Macaca fascicularis (n=4) were inoculated intravenously with P. knowlesi Malayan strain cryo-preserved salivary gland sporozoites, obtained from Anopheles dirus infected with parasites from the Pk1A+ clone and previously confirmed in E30, E06 and E07 for their infectivity of macaques. The P. knowlesi sporozoites stocks had been generated, isolated and cryopreserved at the Centers for Disease Control and Prevention, and then stored at Yerkes. The experiment was designed to contain one baseline time point seven days prior to sporozoite inoculation, six time points after inoculation and terminal necropsies (for pathology studies) scheduled after peaking parasitemias. Venous whole blood and bone marrow aspirate samples were collected at time points to profile for clinical, hematological, parasitological, immunological, functional genomics, proteomics, and metabolomics measurements. A single sub-curative dose of chloroquine was administered via I.M. to the M. mulatta animals at the rise of the infection to dampen the high predictably lethal parasitemias in this species. A subsequent time point was collected to examine the effect of chloroquine on host pathways and whether the M. mulatta host responses became similar to the naturally controlling M. fascicularis host responses. Daily collection of capillary samples was performed for the clinical measurement of complete blood counts, reticulocytes, parasitemias and for sample banking. Within the MaHPIC, this project is known as 'Experiment 33'. This dataset was produced by Monica Cabrera-Mora and Chester J Joyner at the Yerkes Primate Research Center at Emory University. To access other publicly available results from 'E33' and other MaHPIC Experiments, including clinical results (specifics on drugs administered, diet, and veterinary interventions), and other omics, visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC) and the MRMC Office of Research Protection Animal Care and Use Review Office (ACURO).

Available Datasets: 

Experiment 34

Title: Experiment 34: Control necropsy of a mixed cohort of Macaca mulatta and Macaca fascicularis to produce a set of normal clinical, hematological, immunological and omics measures, and normal tissue samples for histological comparison
Description:  A mixed cohort of six malaria-naive male Macaca mulatta (n=3) and Macaca fascicularis (n=3) were necropsied to provide normal tissue samples as controls for the analysis of MaHPIC infection experiments involving these macaque species. Venous whole blood and bone marrow aspirate samples were collected at necropsy to profile clinical, hematological, immune response and functional genomics measurements. Plasma samples were also banked for proteomics and metabolomics measurements, rectal swabs for microbiome studies, and a panel of tissue samples for histological comparisons. Within the MaHPIC, this project is known as 'Experiment 34'. This dataset was produced by Monica Cabrera-Mora at Emory University. To access other publicly available results from E34 and other MaHPIC experiments, including clinical results (specifics on drugs administered, diet, and veterinary interventions), and other omics, visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC) and the MRMC Office of Research Protection Animal Care and Use Review Office (ACURO).
Available Datasets:

Experiment 35

Title: Macaca mulatta infected with Plasmodium coatneyi Hackeri strain to produce and integrate clinical, hematological, parasitological, and omics measures of acute, recrudescent, and chronic infections.

Description: A mixed cohort of seven malaria-naive male Macaca mulatta (n=3) and Macaca fascicularis (n=4) were inoculated intravenously with P. knowlesi Malayan strain cryo-preserved salivary gland sporozoites, obtained from Anopheles dirus infected with parasites from the Pk1A+ clone and previously confirmed in E30, E06, E07, and E34 for their infectivity of macaques. The P. knowlesi sporozoites stocks had been generated, isolated and cryopreserved at the Centers for Disease Control and Prevention, and then stored at Yerkes. The experiment was designed to contain two baseline time points at days -13 and -42 prior to sporozoite inoculation, four (M. mulatta) or six (M. fascicularis) time points after inoculation, plus terminal necropsies (for pathology studies) scheduled between days 48-50 at a time when all animals had chronic infections. Venous whole blood and bone marrow aspirate samples were collected at all time points for clinical, hematological, parasitological, immunological, functional genomics, proteomics, and metabolomics measurements, or sample storage for future testing. Sub-curative doses of artemether were administered via I.M. to the M. mulatta animals at the initial high parasitemia and subsequent lower rises of parasitemias when necessary to dampen the parasitemias and allow a chronic infection to develop. No subcurative doses of artemether were needed for the M. fascicularis, which naturally controlled their parasitemias from the time of the first rise of parasites in the blood. Daily collection of capillary samples was performed for the clinical measurement of complete blood counts, reticulocytes, and parasitemias, and for sample banking. Within the MaHPIC, this project is known as 'Experiment 35'. This dataset was produced by Monica Cabrera-Mora at Emory University. To access other publicly available results from E35 and other MaHPIC experiments, including clinical results (specifics on drugs administered, diet, and veterinary interventions), and other omics, visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public. The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC) and the MRMC Office of Research Protection Animal Care and Use Review Office (ACURO).

Available Datasets: 

 Experiment HuA

Title: Metabolomics of plasma samples from humans infected with Plasmodium vivax.
Description: Patients with vivax malaria were enrolled in this study from June 2011 to December 2012 at the Fundacão de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD), an infectious disease referral center located in Manaus, Western Brazilian Amazon. This study, which required a 42-day follow-up period, was approved by the FMT-HVD Institutional Review Board and the Brazilian National Ethics Committee (CONEP) (IRB approval #: CAAE: 12516713.8.0000.0005). All protocols and documentation were reviewed and sample shipments approved by the Emory IRB. Male and female patients were eligible for inclusion if aged 6 months to 60 years, bodyweight ≥5 kg, presenting a blood parasite density from 250 to 100,000 parasites/microliter and axillary temperature ≥37.5°C or history of fever in the last 48 hours. Exclusion criteria were: use of antimalarials in the previous 30 days, refusal to be followed up for 42 days and any clinical complication. Patients received supervised treatment with 25 mg/kg of chloroquine (CQ) phosphate over a 3-day period (10 mg/kg on day 0 and 7.5 mg/kg on days 1 and 2). Primaquine (0.5 mg/kg per day for 7 days) was prescribed at the end of the 42-day follow-up period. Patients who vomited the first dose within 30 minutes after drug ingestion were re-treated with the same dose. Patients were evaluated on days 0, 1, 2, 3, 7, 14, 28 and 42 and, if they felt ill, at any time during the study period. Blood smear readings, complete blood counts, and diagnostic polymerase chain reaction (PCR) amplifications were performed at all time points. Three aliquots of 100 µL of whole blood from the day of a recurrence were spotted onto filter paper for later analysis by high performance liquid chromatography (HPLC) to estimate the levels of CQ and desethylchloroquine (DCQ) as previously described. In this study, CQ-resistance with parasitological failure was defined as parasite recurrence in the presence of plasma concentrations of CQ and DSQ higher than 100 ng/mL and microsatellite analysis revealing the presence of the same clonal nature at diagnosis and recurrence. The CQ-sensitive control group consisted of patients with no parasitemia recurring during follow-up period. A group of 20 healthy individuals from Brazil was used as non-malarial control group. Samples were obtained in collaboration with Wuelton M. Monteiro (Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil and Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil) and Marcus V.G. Lacerda (Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil and Instituto Leônidas & Maria Deane (FIOCRUZ), Manaus, Amazonas, Brazil).  Metabolomics results were produced by Dean Jones at Emory University.
Available Datasets:  Experiment HuB

 

Title: Metabolomics of plasma samples from humans infected with P.falciparum and P. vivax 

Description: This study is based on archived plasma from samples collected between 2011 and 2014. Patients in Thailand who were infected with P. falciparum (30 subjects), P. vivax (30 subjects), co-infected with P. falciparum and P. vivax (22 subjects) were included, alongside two sets of non-malaria cases: non-malarial febrile illnesses (30 subjects) and healthy controls (30 subjects).  Malaria subjects were enrolled under ethics research protocol TMEC 11-033, and non-malaria cases were enrolled under TMEC 14-025, both approved by the Ethical Review Committee of the Faculty of Tropical Medicine, Mahidol University, Thailand.  All protocols and documentation were reviewed and sample shipments approved by the Emory IRB. Subjects were enrolled at the Ministry of Public Health (MOPH) Malaria Clinics in the Kanchanaburi and Tak provinces clinic between August 2011 and August 2014.  Patients were all adults, at least 18 years old, and not pregnant.  Individuals were not treated prior to sample collection.  Individuals with uncomplicated malaria cases were recruited for the study. Patients were parasitemic and symptomatic at admission, including some being febrile, but all lacked complications of severe malaria, according to WHO guidelines. Cases of non-malaria febrile illness (NMFI) were recruited as controls from the Fever Clinic of the Hospital for Tropical Diseases at Mahidol University.  These individuals were febrile and were malaria-negative by thick smear microscopy and PCR, and had no history of taking antimalarial or antibiotic medications during the two weeks prior to their hospital visit.  The NFMI cases were diagnosed as dengue, influenza, co-infection of the two pathogens, or unidentified febrile illness.  Healthy individuals were also recruited at the Hospital for Tropical Diseases as a control group.  They were afebrile, had no reported history of malaria infection or treatment, were malaria-negative as determined by thick smear and PCR, and were not on any medications. For healthy and NFMI samples, one mL of venous blood was collected in a heparin tube and plasma was aliquoted and frozen at -80C. For malaria patients, one mL of venous blood was collected in either a heparin or ACD tube, frozen, thawed for aliquoting, and refrozen again. A frozen aliquot was shipped on dry ice to Emory University for high-resolution mass spectrometry and metabolomics analyses. Within the MaHPIC, this project is known as ‘Experiment HuB’.  Samples were obtained in collaborations with Jetsumon Prachumsri, Rapathborn Patrapuvich, Viravarn Luvira, Siriwan Rungin, Teerawat Saeseu, and Nattawan Rachaphaew at the Mahidol Vivax Research Unit and the Hospital for Tropical Diseases at Mahidol University.  

 

Available Datasets:

 

 

Experiment HuC

Title: Metabolomics of plasma samples from human volunteers infected with Plasmodium vivax

Description: Sixteen healthy volunteers, 7 malaria naïve and 9 semi-immune, aged 18-45 years, were enrolled in this study during October 2012 to November 2013. Malaria-naïve volunteers were recruited in Cali, Colombia, a non-endemic city; those with previous malaria experience were recruited in Buenaventura, a malaria-endemic area on the Colombian Pacific Coast. The study was approved by Institutional Review Boards (IRB) of the Malaria Vaccine and Drug Development Center–MVDC (CECIV, Cali) and Centro Médico Imbanaco (Cali).  All protocols and documentation were reviewed and samples shipments approved by the Emory IRB.  Male and female patients were eligible for inclusion, which included two steps: 1) age between 15-60 years, hemoglobin levels > 9g/dL, presence of current P. vivax infection, absence of other Plasmodium species determined by thick blood smear and PCR, blood parasite count of 0.1% or more, absence of other acute or chronic diseases, being able to sign an informed consent form; 2) healthy 18 to 45 years old man or non-pregnant women,  capacity to sign an informed consent in a free and voluntary way, acceptable understanding of the clinical trial through the approval of a questionnaire regarding the information given in the consent process, obligatory use of adequate contraceptive method from beginning of recruitment and screening time up to three months after last immunization, do not have chronic or acute diseases, accept not traveling to malaria endemic areas during the clinical trial, have telephone at home or mobile phone that permit permanent contact for follow up, being willing to participated during both steps of the clinical trial. Exclusion criteria included pregnancy, abnormal laboratory test values, hemoglobin pathology, glucose-6-phosphate dehydrogenase (G6PDH) deficiency, positive for blood bank infectious diseases (syphilis, HIV, Chagas disease, HTLV 1–2, and hepatitis B and hepatitis C), or have any condition that would increase the risk of an adverse outcome.  Volunteers were infected with P. vivax via sporozoite challenge by exposing volunteers to bites of 2–4 mosquitoes (Anopheles albimanus) of the same infected batch. Plasma samples were collected at 4 time points: Baseline, 1 month pre-inoculation; Diagnosis; 3 weeks post-treatment; 4 months post-treatment. As soon as parasites were detected by thick blood smears, participants were treated orally with curative doses of chloroquine (1500 mg chloroquine provided in three doses: 600 mg initially then 450 mg doses at 24 and 48 hours) and primaquine (30 mg dose given once per day for 14 days). Clinical trial registration: NCT01585077. Samples were analyzed with liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS), evaluated in a time course and between naïve and semi-immune volunteers.  Within the MaHPIC, this project is known as ‘Experiment HuC’.  Samples were obtained in collaboration with Socrates Herrera from the Malaria Vaccine and Drug Development Center, Colombia.  Metabolomics results were produced by Dean Jones at Emory University. 

Available Datasets:

• Metabolomics - Available at MetaboLights

Supporting Experiment S05

Title:  Investigation of P. vivax trophozoite-schizont transition proteome

Description: The apicomplexan parasite Plasmodium vivax reportedly caused 13.8 million cases of vivax malaria in 2015. Much of the unique biology of this pathogen remains unknown. To expand our proteomics interrogation of the blood-stage interaction with its host animal model Saimiri boliviensis, we analyzed the proteome of infected host reticulocytes undergoing transition from the trophozoite to schizont stages. Two biological replicates analyzed using five database search engines identified 1923 P. vivax and 3188 S. boliviensis proteins.  Within the MaHPIC, this project is known as 'Integral Supporting Project 05 (S05)'.  This dataset was produced by Dave Anderson at SRI International. 

Available Datasets:

 Supporting Experiment S01

Title: Macaca mulatta infected with Plasmodium knowlesi Pk1(A+), Pk1(B+)1+, Pk1(C+) ex vivo time course.

Description: Malaria-naive rhesus macaques (Macaca mulatta), were inoculated with a particular parasite clone and allowed to reach a targeted peak parasitemia of 5% - 10% proportion of infected RBCs. Whole blood was collected at the early ring stage while subjects were under anesthesia, and an ex vivo culture was established using standard protocols, which include but are not limited to the processing of the whole blood by removing platelets and white blood cells. Samples were collected starting at 1.5-2 hours after establishing cultures, followed by collections every 4 hours for a 24-hour period. Blood-stage curative doses of the anti-malarial drug chloroquine were administered to all subjects after whole blood extraction from each subject. Parasitemias were monitored daily by ear sticks. Within the MaHPIC, this project is known as ‘Supporting Project 01’. To access other publicly available results from 'S01' including proteomics and other MaHPIC Experiments, visit http://plasmodb.org/plasmo/mahpic.jsp. This page will be updated as datasets are released to the public.  The experimental design and protocols for this study were approved by the Emory University Institutional Animal Care and Use Committee (IACUC).

Available Datasets: