scholarly journals THE QUEST FOR BUILDING LABORATORY CAPACITY TO SUPPORT CONTROLLED HUMAN MALARIA INFECTION (CHMI) STUDIES IN SUB-SAHARAN AFRICA: EXPERIENCE WITH FIVE SITES

2017 ◽  
Vol 2 (Suppl 2) ◽  
pp. A19.2-A19
Author(s):  
Kennedy Awuondo ◽  
Daniel Njenga ◽  
Elizabeth Nyakarungu ◽  
Pauline Titus ◽  
Awalludin Sutamihardja ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Sub Saharan Africa ◽  
Human Malaria ◽  
Laboratory Capacity ◽  
Controlled Human Malaria Infection ◽  
Sub Saharan

scholarly journals Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis

mSphere ◽  
2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Joshua M. Obiero ◽  
Joseph J. Campo ◽  
Anja Scholzen ◽  
Arlo Randall ◽  
Else M. Bijker ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Vaccine Development ◽  
Antibody Responses ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Human Malaria ◽  
Low Responders ◽  
Controlled Human Malaria Infection ◽  
Auc Value ◽  
High Responders

ABSTRACTImmunization with sporozoites under chloroquine chemoprophylaxis (CPS) induces distinctly preerythrocytic and long-lasting sterile protection against homologous controlled human malaria infection (CHMI). To identify possible humoral immune correlates of protection, plasma samples were collected from 38 CPS-immunized Dutch volunteers for analysis using a wholePlasmodium falciparumproteome microarray with 7,455 full-length or segmented protein features displaying about 91% of the totalP. falciparumproteome. We identified 548 reactive antigens representing 483 unique proteins. Using the breadth of antibody responses for each subject in a mixture-model algorithm, we observed a trimodal pattern, with distinct groups of 16 low responders, 19 medium responders, and 3 high responders. Fifteen out of 16 low responders, 12 of the 19 medium responders, and 3 out of 3 high responders were fully protected from a challenge infection. In the medium-responder group, we identified six novel antigens associated with protection (area under the curve [AUC] value of ≥0.75;P < 0.05) and six other antigens that were specifically increased in nonprotected volunteers (AUC value of ≤0.25;P < 0.05). When used in combination, the multiantigen classifier predicts CPS-induced protective efficacy with 83% sensitivity and 88% specificity. The antibody response patterns characterized in this study represent surrogate markers that may provide rational guidance for clinical vaccine development.IMPORTANCEInfection byPlasmodiumparasites has been a major cause of mortality and morbidity in humans for thousands of years. Despite the considerable reduction of deaths, according to the WHO, over 5 billion people are still at risk, with about 216 million worldwide cases occurring in 2016. More compelling, 15 countries in sub-Saharan Africa bore 80% of the worldwide malaria burden. Complete eradication has been challenging, and the development of an affordable and effective vaccine will go a long way in achieving elimination. However, identifying vaccine candidate targets has been difficult. In the present study, we use a highly effective immunization protocol that confers long-lasting sterile immunity in combination with a wholeP. falciparumproteome microarray to identify antibody responses associated with protection. This study characterizes a novel antibody profile associated with sterile protective immunity and trimodal humoral responses that sheds light on the possible mechanism of CPS-induced immunity againstP. falciparumparasites.

Stratifying Sepsis in Uganda Using Rapid Pathogen Diagnostics and Clinical Data: A Prospective Cohort Study

2021 ◽  
Author(s):  
Matthew J. Cummings ◽  
Barnabas Bakamutumaho ◽  
Nicholas Owor ◽  
John Kayiwa ◽  
Joyce Namulondo ◽  
...  
Keyword(s):  
Prospective Cohort ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Sub Saharan Africa ◽  
Rapid Diagnostics ◽  
Suspected Sepsis ◽  
Laboratory Capacity ◽  
Antimicrobial Management ◽  
Sub Saharan ◽  
Tb 32

The global burden of sepsis is concentrated in sub-Saharan Africa, where extensive pathogen diversity and limited laboratory capacity challenge targeted antimicrobial management of life-threatening infections. In this context, established and emerging rapid pathogen diagnostics may stratify sepsis patients into subgroups with prognostic and therapeutic relevance. In a prospective cohort of adults (age ≥18 years) hospitalized with suspected sepsis in Uganda, we stratified patients using rapid diagnostics for HIV, tuberculosis (TB), malaria, and influenza, and compared clinical characteristics and 30-day outcomes across these pathogen-driven subgroups. From April 2017 to August 2019, 301 adults were enrolled (median age, 32 years [interquartile range, 26–42 years]; female, n = 178 [59%]). A total of 157 patients (53%) were HIV infected. Sixty-one patients (20%) tested positive for malaria, 52 (17%), for TB (including 49 of 157 [31%] HIV-infected patients), and 17 (6%), for influenza. Co-infection was identified in 33 (11%) patients. The frequency of multi-organ failure, including shock and acute respiratory failure, was greatest among patients with HIV-associated TB. Mortality at 30 days was 19% among patients with malaria, 40% among patients with HIV-associated TB, 32% among HIV-infected patients without microbiological evidence of TB, 6% among patients with influenza, and 11% among patients without a pathogen identified. Despite improvements in anti-retroviral delivery, the burden of sepsis in Uganda remains concentrated among young, HIV-infected adults, with a high incidence of severe HIV-associated TB. In parallel with improvements in acute-care capacity, use of rapid pathogen diagnostics may enhance triage and antimicrobial management during emergency care for sepsis in sub-Saharan Africa, and could be used to enrich study populations when trialing pathogen-specific treatment strategies in the region.

scholarly journals Immunoprofiles associated with controlled human malaria infection and naturally acquired immunity identify a shared IgA pre-erythrocytic immunoproteome

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Andrea A. Berry ◽  
Joshua M. Obiero ◽  
Mark A. Travassos ◽  
Amed Ouattara ◽  
Drissa Coulibaly ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Vaccine Development ◽  
Protein Microarray ◽  
Antibody Responses ◽  
Liver Stage ◽  
Human Malaria ◽  
Controlled Human Malaria Infection ◽  
Iga Antibody ◽  
Potential Vaccine ◽  
Antigen Protein

AbstractKnowledge of the Plasmodium falciparum antigens that comprise the human liver stage immunoproteome is important for pre-erythrocytic vaccine development, but, compared with the erythrocytic stage immunoproteome, more challenging to classify. Previous studies of P. falciparum antibody responses report IgG and rarely IgA responses. We assessed IgG and IgA antibody responses in adult sera collected during two controlled human malaria infection (CHMI) studies in malaria-naïve volunteers and in 1- to 6-year-old malaria-exposed Malian children on a 251 P. falciparum antigen protein microarray. IgG profiles in the two CHMI groups were equivalent and differed from Malian children. IgA profiles were robust in the CHMI groups and a subset of Malian children. We describe immunoproteome differences in naïve vs. exposed individuals and report pre-erythrocytic proteins recognized by the immune system. IgA responses detected in this study expand the list of pre-erythrocytic antigens for further characterization as potential vaccine candidates.

scholarly journals Outcomes of controlled human malaria infection after BCG vaccination

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jona Walk ◽  
L. Charlotte J. de Bree ◽  
Wouter Graumans ◽  
Rianne Stoter ◽  
Geert-Jan van Gemert ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Human Malaria ◽  
Bcg Vaccination ◽  
Controlled Human Malaria Infection

scholarly journals Mosquito Bite-Induced Controlled Human Malaria Infection withPlasmodium vivaxorP. falciparumGenerates Immune Responses to Homologous and Heterologous Preerythrocytic and Erythrocytic Antigens

2018 ◽  
Vol 87 (3) ◽  
Author(s):  
Cysha E. Hall ◽  
Lisa M. Hagan ◽  
Elke Bergmann-Leitner ◽  
Donna M. Tosh ◽  
Jason W. Bennett ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Similar Proportion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Content Type ◽  
Human Malaria ◽  
Before And After ◽  
Controlled Human Malaria Infection

ABSTRACTSeroepidemiological studies on the prevalence of antibodies to malaria antigens are primarily conducted on individuals from regions of endemicity. It is therefore difficult to accurately correlate the antibody responses to the timing and number of prior malaria infections. This study was undertaken to assess the evolution of antibodies to the dominant surface antigens ofPlasmodium vivaxandP. falciparumfollowing controlled human malaria infection (CHMI) in malaria-naive individuals. Serum samples from malaria-naive adults, collected before and after CHMI with eitherP. vivax(n= 18) orP. falciparum(n= 18), were tested for the presence of antibodies to the circumsporozoite protein (CSP) and the 42-kDa fragment of merozoite surface protein 1 (MSP-142) ofP. vivaxandP. falciparumusing an enzyme-linked immunosorbent assay (ELISA). Approximately 1 month following CHMI with eitherP. vivaxorP. falciparum, >60% of subjects seroconverted to homologous CSP and MSP-1. More than 50% of the subjects demonstrated reactivity to heterologous CSP and MSP-142, and a similar proportion of subjects remained seropositive to homologous MSP-142>5 months after CHMI. Computational analysis provides insight into the presence of cross-reactive responses. The presence of long-lived and heterologous reactivity and its functional significance, if any, need to be taken into account while evaluating malaria exposure in field settings.

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