Differential Expression of var Gene Groups Is Associated with Morbidity Caused by Plasmodium falciparum Infection in Tanzanian Children

ABSTRACT The var gene family of Plasmodium falciparum encodes the variant surface antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 is considered an important pathogenicity factor in P. falciparum infection because it mediates cytoadherence to host cell endothelial receptors. var genes can be grouped into three major groups, A, B, and C, and the conserved var genes, var1-4, according to sequence similarities in coding and noncoding upstream regions. Using real-time quantitative PCR in a study conducted in Tanzania, the var transcript abundances of the different var gene groups were compared among patients with severe, uncomplicated, and asymptomatic malaria. Transcripts of var group A and B genes were more abundant in patients with severe malaria than in patients with uncomplicated malaria. In general, the transcript abundances of var group A and B genes were higher for children with clinical malaria than for children with asymptomatic infections. The var group C and var1-like transcript abundances were similar between the three sample groups. A transcript abundance pattern similar to that for var group A was observed for var2csa and var3-like genes. These results suggest that substantial and systematic differences in var gene expression exist between different clinical presentations.

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Genotyping cognate Plasmodium falciparum in humans and mosquitoes to estimate onward transmission of asymptomatic infections

Nature Communications ◽

10.1038/s41467-021-21269-2 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 2

Author(s):

Kelsey M. Sumner ◽

Elizabeth Freedman ◽

Lucy Abel ◽

Andrew Obala ◽

Brian W. Pence ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Odds Ratio ◽

Asymptomatic Malaria ◽

Major Contributor ◽

Western Kenya ◽

High Transmission ◽

Transmission Reduction ◽

Asymptomatic Infections ◽

Infection Types ◽

Natural Settings

AbstractMalaria control may be enhanced by targeting reservoirs of Plasmodium falciparum transmission. One putative reservoir is asymptomatic malaria infections and the scale of their contribution to transmission in natural settings is not known. We assess the contribution of asymptomatic malaria to onward transmission using a 14-month longitudinal cohort of 239 participants in a high transmission site in Western Kenya. We identify P. falciparum in asymptomatically- and symptomatically-infected participants and naturally-fed mosquitoes from their households, genotype all parasites using deep sequencing of the parasite genes pfama1 and pfcsp, and use haplotypes to infer participant-to-mosquito transmission through a probabilistic model. In 1,242 infections (1,039 in people and 203 in mosquitoes), we observe 229 (pfcsp) and 348 (pfama1) unique parasite haplotypes. Using these to link human and mosquito infections, compared with symptomatic infections, asymptomatic infections more than double the odds of transmission to a mosquito among people with both infection types (Odds Ratio: 2.56; 95% Confidence Interval (CI): 1.36–4.81) and among all participants (OR 2.66; 95% CI: 2.05–3.47). Overall, 94.6% (95% CI: 93.1–95.8%) of mosquito infections likely resulted from asymptomatic infections. In high transmission areas, asymptomatic infections are the major contributor to mosquito infections and may be targeted as a component of transmission reduction.

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PO 8419 SPATIO-TEMPORAL MAPPING OF ASYMPTOMATIC AND CLINICAL MALARIA INFECTIONS REVEALS FOCI OF MALARIA TRANSMISSION FOR TARGETED CONTROL INTERVENTIONS

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.91 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A35.2-A35

Author(s):

Makhtar Niang ◽

Cheikh Talla ◽

Nafissatou Diagne ◽

Fatoutama Diene-Sarr ◽

Cheikh Sokhna

Keyword(s):

Malaria Transmission ◽

Malaria Incidence ◽

Clinical Malaria ◽

Asymptomatic Malaria ◽

Design Strategies ◽

Cross Sectional ◽

Asymptomatic Infections ◽

Spatio Temporal ◽

Malaria Episodes

BackgroundThe global decline of malaria incidence over the past decade has led to the thought that elimination could be achieved. This has resulted in an increased interest to design strategies to target the hidden reservoir of asymptomatic infections among populations and interrupt on-going residual local malaria transmission. This study explored the reservoir of asymptomatic Plasmodium infections and its relationship with subsequent clinical malaria infections in low-transmission areas in Senegal.MethodsCross-sectional surveys were carried out in 2013, 2014, 2015, and 2016 and combined with longitudinal follow-up to determine and geolocalise both asymptomatic and clinical malaria episodes in Dielmo and Ndiop, Senegal. The prevalence of asymptomatic Plasmodium carriage in the community was investigated by real-time PCR while clinical malaria attacks were identified at health facilities during the transmission season. All households were georeferenced to spatially map asymptomatic and clinical infections.ResultsThe study revealed substantial asymptomatic infections with average parasite carriage of 8.11% and 7% in Dielmo and Ndiop, respectively. P. falciparum accounted for most asymptomatic infections (more than 90%). In Dielmo, 95% of asymptomatic infections clustered within the same geographical areas while infections were disparate in Ndiop. Preliminary fine-scale mapping of asymptomatic and clinical malaria infections identified clusters of higher malaria incidence interpreted as foci of transmission across the four-year study period with 95%–98% of clinical infections occurring in households where an asymptomatic malaria infection existed.ConclusionThis study revealed substantial asymptomatic Plasmodium infections in both settings throughout the four-year study period and spatial clusters of malaria infections at the microepidemiological level. Together, these findings could offer a feasible approach for a rational targeting of malaria control interventions to achieve elimination.

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Faculty Opinions recommendation of Antibodies to pre-erythrocytic Plasmodium falciparum antigens and risk of clinical malaria in Kenyan children.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1112025.567992 ◽

2008 ◽

Author(s):

Rosanna Peeling ◽

Jane Cunningham

Keyword(s):

Plasmodium Falciparum ◽

Clinical Malaria

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Faculty Opinions recommendation of RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: a case-control study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736423511.793573188 ◽

2020 ◽

Author(s):

Toshihiro Horii ◽

Nirianne Palacpac

Keyword(s):

Plasmodium Falciparum ◽

Case Control Study ◽

Clinical Malaria ◽

Case Control ◽

Antibody Responses ◽

African Children ◽

Control Study

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Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽

10.1182/blood.v76.6.1250.1250 ◽

1990 ◽

Vol 76 (6) ◽

pp. 1250-1255 ◽

Cited By ~ 36

Author(s):

S Whitehead ◽

TE Peto

Keyword(s):

Plasmodium Falciparum ◽

Growth Inhibition ◽

Antimalarial Activity ◽

Clinical Malaria ◽

Inhibitory Effect ◽

Parasite Development ◽

And Control ◽

Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

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Changes in Antigen-Specific Cytokine and Chemokine Responses to Plasmodium falciparum Antigens in a Highland Area of Kenya after a Prolonged Absence of Malaria Exposure

Infection and Immunity ◽

10.1128/iai.01924-14 ◽

2014 ◽

Vol 82 (9) ◽

pp. 3775-3782 ◽

Cited By ~ 6

Author(s):

Lyticia A. Ochola ◽

Cyrus Ayieko ◽

Lily Kisia ◽

Ng'wena G. Magak ◽

Estela Shabani ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Severe Disease ◽

Clinical Malaria ◽

Necrosis Factor Alpha ◽

Content Type ◽

Highland Area ◽

Cytokine Responses ◽

Increased Risk ◽

Tnf Α ◽

Ifn Γ

ABSTRACTIndividuals naturally exposed toPlasmodium falciparumlose clinical immunity after a prolonged lack of exposure.P. falciparumantigen-specific cytokine responses have been associated with protection from clinical malaria, but the longevity ofP. falciparumantigen-specific cytokine responses in the absence of exposure is not well characterized. A highland area of Kenya with low and unstable malaria transmission provided an opportunity to study this question. The levels of antigen-specific cytokines and chemokines associated in previous studies with protection from clinical malaria (gamma interferon [IFN-γ], interleukin-10 [IL-10], and tumor necrosis factor alpha [TNF-α]), with increased risk of clinical malaria (IL-6), or with pathogenesis of severe disease in malaria (IL-5 and RANTES) were assessed by cytometric bead assay in April 2008, October 2008, and April 2009 in 100 children and adults. During the 1-year study period, none had an episode of clinicalP. falciparummalaria. Two patterns of cytokine responses emerged, with some variation by antigen: a decrease at 6 months (IFN-γ and IL-5) or at both 6 and 12 months (IL-10 and TNF-α) or no change over time (IL-6 and RANTES). These findings document thatP. falciparumantigen-specific cytokine responses associated in prior studies with protection from malaria (IFN-γ, TNF-α, and IL-10) decrease significantly in the absence ofP. falciparumexposure, whereas those associated with increased risk of malaria (IL-6) do not. The study findings provide a strong rationale for future studies of antigen-specific IFN-γ, TNF-α, and IL-10 responses as biomarkers of increased population-level susceptibility to malaria after prolonged lack ofP. falciparumexposure.

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Molecular and Biochemical Analysis of Periplastidial Starch Metabolism in the Cryptophyte Guillardia theta

Eukaryotic Cell ◽

10.1128/ec.00381-05 ◽

2006 ◽

Vol 5 (6) ◽

pp. 964-971 ◽

Cited By ~ 12

Author(s):

Ilka Haferkamp ◽

Philippe Deschamps ◽

Michelle Ast ◽

Wolfgang Jeblick ◽

Uwe Maier ◽

...

Keyword(s):

Continuous Light ◽

Subcellular Location ◽

Transcript Abundance ◽

Transport Processes ◽

Phosphate Transporter ◽

Light Phase ◽

Abundance Pattern ◽

Total Enzyme Activity ◽

Triose Phosphate ◽

Guillardia Theta

ABSTRACT Starch in synchronously grown Guillardia theta cells accumulates throughout the light phase, followed by a linear degradation during the night. In contrast to the case for other unicellular algae such as Chlamydomonas reinhardtii, no starch turnover occurred in this organism under continuous light. The gene encoding granule-bound starch synthase (GBSS1), the enzyme responsible for amylose synthesis, displays a diurnal expression cycle. The pattern consisted of a maximal transcript abundance around the middle of the light phase and a very low level during the night. This diurnal regulation of GBSS1 transcript abundance was demonstrated to be independent of the circadian clock but tightly light regulated. A similar yet opposite type of regulation pattern was found for two α-amylase isoforms and for one of the two plastidic triose phosphate transporter genes investigated. In these cases, however, the transcript abundance peaked in the night phase. The second plastidic triose phosphate transporter gene had the GBSS1 mRNA abundance pattern. Quantification of the GBSS1 activity revealed that not only gene expression but also total enzyme activity exhibited a maximum in the middle of the light phase. To gain a first insight into the transport processes involved in starch biosynthesis in cryptophytes, we demonstrated the presence of both plastidic triose phosphate transporter and plastidic ATP/ADP transporter activities in proteoliposomes harboring either total membranes or plastid envelope membranes from G. theta. These molecular and biochemical data are discussed with respect to the environmental conditions experienced by G. theta and with respect to the unique subcellular location of starch in cryptophytes.

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The epidemiology and detectability of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in low, moderate and high transmission settings in Ethiopia

Malaria Journal ◽

10.1186/s12936-021-03587-4 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Elifaged Hailemeskel ◽

Surafel K Tebeje ◽

Sinknesh W. Behaksra ◽

Girma Shumie ◽

Getasew Shitaye ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Plasmodium Vivax ◽

Age Groups ◽

Diagnostic Tools ◽

Asymptomatic Malaria ◽

Rapid Diagnostics ◽

Cross Sectional ◽

Low Transmission ◽

High Transmission ◽

Study Sites

Abstract Background As countries move to malaria elimination, detecting and targeting asymptomatic malaria infections might be needed. Here, the epidemiology and detectability of asymptomatic Plasmodium falciparum and Plasmodium vivax infections were investigated in different transmission settings in Ethiopia. Method: A total of 1093 dried blood spot (DBS) samples were collected from afebrile and apparently healthy individuals across ten study sites in Ethiopia from 2016 to 2020. Of these, 862 were from community and 231 from school based cross-sectional surveys. Malaria infection status was determined by microscopy or rapid diagnostics tests (RDT) and 18S rRNA-based nested PCR (nPCR). The annual parasite index (API) was used to classify endemicity as low (API > 0 and < 5), moderate (API ≥ 5 and < 100) and high transmission (API ≥ 100) and detectability of infections was assessed in these settings. Results In community surveys, the overall prevalence of asymptomatic Plasmodium infections by microscopy/RDT, nPCR and all methods combined was 12.2% (105/860), 21.6% (183/846) and 24.1% (208/862), respectively. The proportion of nPCR positive infections that was detectable by microscopy/RDT was 48.7% (73/150) for P. falciparum and 4.6% (2/44) for P. vivax. Compared to low transmission settings, the likelihood of detecting infections by microscopy/RDT was increased in moderate (Adjusted odds ratio [AOR]: 3.4; 95% confidence interval [95% CI] 1.6–7.2, P = 0.002) and high endemic settings (AOR = 5.1; 95% CI 2.6–9.9, P < 0.001). After adjustment for site and correlation between observations from the same survey, the likelihood of detecting asymptomatic infections by microscopy/RDT (AOR per year increase = 0.95, 95% CI 0.9–1.0, P = 0.013) declined with age. Conclusions Conventional diagnostics missed nearly half of the asymptomatic Plasmodium reservoir detected by nPCR. The detectability of infections was particularly low in older age groups and low transmission settings. These findings highlight the need for sensitive diagnostic tools to detect the entire parasite reservoir and potential infection transmitters.

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Understanding adherence to reactive treatment of asymptomatic malaria infections in The Gambia

Scientific Reports ◽

10.1038/s41598-021-81468-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Fatou Jaiteh ◽

Joseph Okebe ◽

Yoriko Masunaga ◽

Umberto D’Alessandro ◽

Jane Achan ◽

...

Keyword(s):

Day Treatment ◽

Treatment Completion ◽

Clinical Malaria ◽

Research Process ◽

The Gambia ◽

Individual Compound ◽

Asymptomatic Malaria ◽

High Coverage ◽

Major Health Problem ◽

The Impact

AbstractThe impact of different types of reactive case detection and/or treatment strategies for malaria elimination depends on high coverage and participants’ adherence. However, strategies to optimise adherence are limited, particularly for people with asymptomatic or no infections. As part of a cluster-randomized trial to evaluate the effect of reactive treatment in The Gambia, all residents in the compound of a diagnosed clinical malaria patient received dihydro-artemisinin–piperaquine (DP). Using a mixed method approach, we assessed which factors contribute to adherence among the contacts of malaria cases that showed no symptoms. Adherence was defined as the proportion of compound members that (1) returned all medicine bags empty and (2) self-reported (3-day) treatment completion. Among the 273 individuals from 14 compounds who received DP, 227 (83.1%) were available for and willing to participate in the survey; 85.3% (233/273) returned empty medicine bags and 91.6% (208/227) self-reported treatment completion. Although clinical malaria was not considered a major health problem, reported adherence was high. The drivers of adherence were the strong sense of responsibility towards protecting the individual, compound and the village. Adherence can be optimised through a transdisciplinary implementation research process of engaging communities to bridge the gap between research goals and social realities.

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