• COVID-19 Outbreaks in US Immigrant Detention Centers: The Urgent Need to Adopt CDC Guidelines for Prevention and Evaluation.

      Openshaw, John J; Travassos, Mark A (Oxford University Press, 2021-01-23)
      There have been several significant outbreaks of COVID-19 in federal immigrant detention centers, which lack clear and consistent guidelines across Department of Homeland Security (DHS) agencies to limit the spread of COVID-19. The Centers for Disease Control and Prevention (CDC) has issued detailed guidelines for the control, prevention, and evaluation of COVID-19 in detention facilities. Although the DHS's Immigration and Customs Enforcement agency has stated that it complies with CDC recommendations, its policies significantly differ from these CDC guidelines, placing detainees at risk for contracting COVID-19. This submission urges the adoption of CDC guidelines across DHS-associated facilities. Such a policy change has the potential to protect and save the lives of the most vulnerable populations under the auspices of the federal government.
    • A Decline and Age Shift in Malaria Incidence in Rural Mali following Implementation of Seasonal Malaria Chemoprevention and Indoor Residual Spraying

      Coulibaly, Drissa; Guindo, Boureima; Niangaly, Amadou; Maiga, Fayçal; Konate, Salimata; Kodio, Aly; Diallo, Astou; Antar, Abdou Tahirou Mohamed; Kone, Abdoulaye K; Traore, Karim; et al. (American Society of Tropical Medicine and Hygiene, 2021-03-01)
      Many African countries have reported declines in malaria incidence, attributed to the implementation of control strategies. In Mali, artemisinin-based combination therapy (ACT) was introduced in 2004, and long-lasting insecticide-treated nets (LLINs) have been partially distributed free of charge since 2007. In the Malian town of Bandiagara, a study conducted from 2009 to 2013 showed a stable incidence of malaria compared with 1999, despite the implementation of ACTs and LLINs. Since 2016, seasonal malaria chemoprevention has been scaled up across the country. In addition to these strategies, the population of Bandiagara benefited from indoor residual spray implementation in 2017 and 2018 and continued universal bed net coverage. This study aimed to measure the incidence of malaria in Bandiagara, given this recent scaling up of control strategies. A cohort of 300 children aged 6 months to 15 years was followed up from October 2017 to December 2018. We performed monthly cross-sectional surveys to measure anemia and the prevalence of malaria infection by microscopy. The overall incidence of symptomatic malaria was 0.5 episodes/person-year. Malaria incidence in children up to 5 years old significantly declined since 2012 and since 1999 (incidence rate ratio estimates: 6.7 [95% CI: 4.2–11.4] and 13.5 [95% CI: 8.4–22.7]), respectively. The average prevalence of malaria parasitemia was 6.7%. Malaria incidence was higher in children older than 5 years than in those younger than 5 years, highlighting the need to extend malaria control efforts to these older children. Copyright © 2021 by The American Society of Tropical Medicine and Hygiene.
    • High-throughput Detection of Eukaryotic Parasites and Arboviruses in Mosquitoes

      Cannon, Matthew V; Bogale, Haikel N; Bhalerao, Devika; Keita, Kalil; Camara, Denka; Barry, Yaya; Keita, Moussa; Coulibaly, Drissa; Kone, Abdoulaye K; Doumbo, Ogobara K; et al. (The Company of Biologists Ltd., 2021-06-22)
      Vector-borne pathogens cause many human infectious diseases and are responsible for high mortality and morbidity throughout the world. They can also cause livestock epidemics with dramatic social and economic consequences. Due to its high costs, vector-borne disease surveillance is often limited to current threats, and the investigation of emerging pathogens typically occurs after the reports of clinical cases. Here, we use high-throughput sequencing to detect and identify a wide range of parasites and viruses carried by mosquitoes from Cambodia, Guinea, Mali and Maryland. We apply this approach to individual Anopheles mosquitoes as well as pools of mosquitoes captured in traps; and compare the outcomes of this assay when applied to DNA or RNA. We identified known human and animal pathogens and mosquito parasites belonging to a wide range of taxa, as well as novel DNA sequences from previously uncharacterized organisms. Our results also revealed that analysis of the content of an entire trap could be an efficient approach to monitor and identify rare vector-borne pathogens in large surveillance studies. Overall, we describe a high-throughput and easy-to-customize assay to screen for a wide-range of pathogens and efficiently complement current vector-borne disease surveillance approaches.
    • Host and Parasite Transcriptomic Changes upon Successive Plasmodium falciparum Infections in Early Childhood

      Bradwell, Katie R; Coulibaly, Drissa; Koné, Abdoulaye K; Laurens, Matthew B; Dembélé, Ahmadou; Tolo, Youssouf; Traoré, Karim; Niangaly, Amadou; Berry, Andrea A; Kouriba, Bourema; et al. (American Society for Microbiology, 2020-08)
      Children are highly susceptible to clinical malaria, and in regions where malaria is endemic, their immune systems must face successive encounters with Plasmodium falciparum parasites before they develop immunity, first against severe disease and later against uncomplicated malaria. Understanding cellular and molecular interactions between host and parasites during an infection could provide insights into the processes underlying this gradual acquisition of immunity, as well as to how parasites adapt to infect hosts that are successively more malaria experienced. Here, we describe methods to analyze the host and parasite gene expression profiles generated simultaneously from blood samples collected from five consecutive symptomatic P. falciparum infections in three Malian children. We show that the data generated enable statistical assessment of the proportions of (i) each white blood cell subset and (ii) the parasite developmental stages, as well as investigations of host-parasite gene coexpression. We also use the sequences generated to analyze allelic variations in transcribed regions and determine the complexity of each infection. While limited by the modest sample size, our analyses suggest that host gene expression profiles primarily clustered by individual, while the parasite gene expression profiles seemed to differentiate early from late infections. Overall, this study provides a solid framework to examine the mechanisms underlying acquisition of immunity to malaria infections using whole-blood transcriptome sequencing (RNA-seq).IMPORTANCE We show that dual RNA-seq from patient blood samples allows characterization of host/parasite interactions during malaria infections and can provide a solid framework to study the acquisition of antimalarial immunity, as well as the adaptations of P. falciparum to malaria-experienced hosts.
    • Immunoprofiles associated with controlled human malaria infection and naturally acquired immunity identify a shared IgA pre-erythrocytic immunoproteome

      Berry, Andrea A; Obiero, Joshua M; Travassos, Mark A; Ouattara, Amed; Coulibaly, Drissa; Adams, Matthew; de Assis, Rafael Ramiro; Jain, Aarti; Taghavian, Omid; Sy, Andrew; et al. (Springer Nature, 2021-09-13)
      Knowledge 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.
    • Inadequate Minority Representation within SARS-CoV-2 Vaccine Trials

      Craft, Joshua F; Travassos, Mark A; Foppiano Palacios, Carlo; Openshaw, John J (American Society of Tropical Medicine and Hygiene, 2020-11-11)
      Minority communities have borne the brunt of COVID-19 disease in the United States. Nonwhites have contracted most of the SARS-CoV-2 infections; COVID-19 mortality rates for Black Americans are more than twice those for whites. Given this, studying the most effective ways to prevent and treat SARS-CoV-2 in these populations should be a research priority, particularly with respect to vaccine trials. Federal guidelines from the National Institutes of Health and Food and Drug Administration emphasize the need for inclusion of minority groups in these trials, but none of the publicly available SARS-CoV-2 vaccine trial protocols requires representative sampling of minorities. This piece emphasizes the importance of adequate inclusion of minority communities in SARS-CoV-2 vaccine trials, and the implications of this inclusion for SARS-CoV-2 vaccine distribution. © 2021 by The American Society of Tropical Medicine and Hygiene
    • Malian adults maintain serologic responses to virulent PfEMP1s amid seasonal patterns of fluctuation

      Ventimiglia, Noah T; Stucke, Emily M; Coulibaly, Drissa; Berry, Andrea A; Lyke, Kirsten E; Laurens, Matthew B; Bailey, Jason A; Adams, Matthew; Niangaly, Amadou; Kone, Abdoulaye K; et al. (Springer Nature, 2021-07-13)
      Plasmodium falciparum erythrocyte membrane protein-1s (PfEMP1s), diverse malaria proteins expressed on the infected erythrocyte surface, play an important role in pathogenesis, mediating adhesion to host vascular endothelium. Antibodies to particular non-CD36-binding PfEMP1s are associated with protection against severe disease. We hypothesized that given lifelong P. falciparum exposure, Malian adults would have broad PfEMP1 serorecognition and high seroreactivity levels during follow-up, particularly to non-CD36-binding PfEMP1s such as those that attach to endothelial protein C receptor (EPCR) and intercellular adhesion molecule-1 (ICAM-1). Using a protein microarray, we determined serologic responses to 166 reference PfEMP1 fragments during a dry and subsequent malaria transmission season in Malian adults. Malian adult sera had PfEMP1 serologic responses throughout the year, with decreased reactivity to a small subset of PfEMP1 fragments during the dry season and increases in reactivity to a different subset of PfEMP1 fragments during the subsequent peak malaria transmission season, especially for intracellular PfEMP1 domains. For some individuals, PfEMP1 serologic responses increased after the dry season, suggesting antigenic switching during asymptomatic infection. Adults were more likely to experience variable serorecognition of CD36-binding PfEMP1s than non-CD36-binding PfEMP1s that bind EPCR or ICAM-1, which remained serorecognized throughout the year. Sustained seroreactivity to non-CD36-binding PfEMP1s throughout adulthood amid seasonal fluctuation patterns may reflect underlying protective severe malaria immunity and merits further investigation.
    • The Mariner

      Travassos, Mark A (Springer Nature, 2021-02-23)
    • STRIDE: a command-line HMM-based identifier and sub-classifier of Plasmodium falciparum RIFIN and STEVOR variant surface antigen families.

      Zhou, Albert E; Shah, Zalak V; Bradwell, Katie R; Munro, James B; Berry, Andrea A; Serre, David; Takala-Harrison, Shannon; O'Connor, Timothy D; Silva, Joana C; Travassos, Mark A (Springer Nature, 2022-01-06)
      Background: RIFINs and STEVORs are variant surface antigens expressed by P. falciparum that play roles in severe malaria pathogenesis and immune evasion. These two highly diverse multigene families feature multiple paralogs, making their classification challenging using traditional bioinformatic methods. Results: STRIDE (STevor and RIfin iDEntifier) is an HMM-based, command-line program that automates the identification and classification of RIFIN and STEVOR protein sequences in the malaria parasite Plasmodium falciparum. STRIDE is more sensitive in detecting RIFINs and STEVORs than available PFAM and TIGRFAM tools and reports RIFIN subtypes and the number of sequences with a FHEYDER amino acid motif, which has been associated with severe malaria pathogenesis. Conclusions: STRIDE will be beneficial to malaria research groups analyzing genome sequences and transcripts of clinical field isolates, providing insight into parasite biology and virulence. © 2021, The Author(s).
    • Successful Profiling of Plasmodium falciparum Gene Expression in Clinical Samples via a Custom Capture Array

      Stucke, Emily M; Dara, Antoine; Dwivedi, Ankit; Hodges, Theresa K; Ott, Sandra; Coulibaly, Drissa; Koné, Abdoulaye K; Traoré, Karim; Guindo, Bouréima; Tangara, Bourama M; et al. (American Society for Microbiology, 2021-11-30)
      var genes encode Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) antigens. These highly diverse antigens are displayed on the surface of infected erythrocytes and play a critical role in immune evasion and sequestration of infected erythrocytes. Studies of var expression using non-leukocyte-depleted blood are challenging because of the predominance of host genetic material and lack of conserved var segments. Our goal was to enrich for parasite RNA, allowing de novo assembly of var genes and detection of expressed novel variants. We used two overall approaches: (i) enriching for total mRNA in the sequencing library preparations and (ii) enriching for parasite RNA with a custom capture array based on Roche's SeqCap EZ enrichment system. The capture array was designed with probes based on the whole 3D7 reference genome and an additional >4,000 full-length var gene sequences from other P. falciparum strains. We tested each method on RNA samples from Malian children with severe or uncomplicated malaria infections. All reads mapping to the human genome were removed, the remaining reads were assembled de novo into transcripts, and from these, var-like transcripts were identified and annotated. The capture array produced the longest maximum length and largest numbers of var gene transcripts in each sample, particularly in samples with low parasitemia. Identifying the most-expressed var gene sequences in whole-blood clinical samples without the need for extensive processing or generating sample-specific reference genome data is critical for understanding the role of PfEMP1s in malaria pathogenesis. IMPORTANCE Malaria parasites display antigens on the surface of infected red blood cells in the human host that facilitate attachment to blood vessels, contributing to the severity of infection. These antigens are highly variable, allowing the parasite to evade the immune system. Identifying these expressed antigens is critical to understanding the development of severe malarial disease. However, clinical samples contain limited amounts of parasite genetic material, a challenge for sequencing efforts further compounded by the extreme diversity of the parasite surface antigens. We present a method that enriches for these antigen sequences in clinical samples using a custom capture array, requiring minimal processing in the field. While our results are focused on the malaria parasite Plasmodium falciparum, this approach has broad applicability to other highly diverse antigens from other parasites and pathogens such as those that cause giardiasis and leishmaniasis.
    • Vaccinating Detained Migrants against SARS-CoV-2 - Preventing Another Tragedy.

      Foppiano Palacios, Carlo; Travassos, Mark A (Massachusetts Medical Society, 2020-12-30)