Transmission Of Plasmodium Parasites Research Articles

Identification of a novel protein localized to the crystalloid of the Plasmodium ookinete

Reducing Plasmodium parasite transmission via the mosquito vector is a promising strategy for malaria control and elimination in endemic regions. In the mosquito midgut after the ingestion of an infected blood meal, malaria parasite gametes egress from erythrocytes and fertilize to develop into motile ookinetes that traverse midgut epithelial cells and transform into oocysts adjacent the basal lamina. Plasmodium ookinetes and young oocysts possess a unique organelle called the crystalloid; which has a honeycomb-like matrix structure and is indicated to be involved in sporozoite formation and maturation. In this study, we identified a novel crystalloid protein, PY17X_1113800, that is exclusively expressed in developing ookinetes. The protein possesses a signal peptide sequence, but lacks a transmembrane domain or GPI anchor signal sequence, as well as predicted adhesive domains which are characterisitic of many crystalloid proteins. The protein is highly conserved across the phylum Apicomplexa and within the greater clade Alveolata, such as Vitrella and the ciliates Paramecium and Tetrahymena, but is absent in cryptosporidia.

Tarsal exposure to atovaquone inhibits chikungunya virus transmission by Aedes aegypti mosquitoes, but not the transmission of Zika virus

The antimalarial drug atovaquone was recently reported to inhibit the in vitro replication of different arboviruses, including chikungunya virus (CHIKV) and Zika virus (ZIKV). Furthermore, atovaquone was shown to block Plasmodium parasite transmission by Anopheles mosquitoes when the mosquitoes were exposed to low concentrations on treated surfaces (i.e. tarsal exposure). Therefore, we evaluated the anti-CHIKV and -ZIKV effects of atovaquone via tarsal exposure in Aedes aegypti mosquitoes. We first confirmed that atovaquone exerted a dose-dependent antiviral effect on CHIKV and ZIKV replication in mosquito-derived cells. The modest antiviral effect could be rescued by adding exogenous uridine. Next, we assessed the effect of tarsal exposure to atovaquone on the fitness of Ae. aegypti. Concentrations up to 100 μmol/m2 did not affect the fecundity and egg-hatching rate. No significant effect on mosquito survival was observed when mosquitoes were exposed to concentrations up to 25 μmol/m2. To evaluate the antiviral effect of atovaquone against CHIKV, we exposed female mosquitoes to 100 μmol/m2 atovaquone for 1h, after which the mosquitoes were immediately infected with CHIKV or ZIKV via bloodmeal. Atovaquone did not significantly reduce ZIKV or CHIKV infection in Ae. aegypti, but successfully blocked the transmission of CHIKV in saliva. Tarsal exposure to antiviral drugs could therefore be a potential new strategy to reduce virus transmission by mosquitoes.

Anopheles vector distribution and malaria transmission dynamics in Gbêkê region, central Côte d’Ivoire

BackgroundA better understanding of vector distribution and malaria transmission dynamics at a local scale is essential for implementing and evaluating effectiveness of vector control strategies. Through the data gathered in the framework of a cluster randomized controlled trial (CRT) evaluating the In2Care (Wageningen, Netherlands) Eave Tubes strategy, the distribution of the Anopheles vector, their biting behaviour and malaria transmission dynamics were investigated in Gbêkê region, central Côte d’Ivoire.MethodsFrom May 2017 to April 2019, adult mosquitoes were collected monthly using human landing catches (HLC) in twenty villages in Gbêkê region. Mosquito species wereidentified morphologically. Monthly entomological inoculation rates (EIR) were estimated by combining the HLC data with mosquito sporozoite infection rates measured in a subset of Anopheles vectors using PCR. Finally, biting rate and EIR fluctuations were fit to local rainfall data to investigate the seasonal determinants of mosquito abundance and malaria transmission in this region.ResultsOverall, Anopheles gambiae, Anopheles funestus, and Anopheles nili were the three vector complexes found infected in the Gbêkê region, but there was a variation in Anopheles vector composition between villages. Anopheles gambiae was the predominant malaria vector responsible for 84.8% of Plasmodium parasite transmission in the area. An unprotected individual living in Gbêkê region received an average of 260 [222–298], 43.5 [35.8–51.29] and 3.02 [1.96–4] infected bites per year from An. gambiae, An. funestus and An. nili, respectively. Vector abundance and malaria transmission dynamics varied significantly between seasons and the highest biting rate and EIRs occurred in the months of heavy rainfall. However, mosquitoes infected with malaria parasites remained present in the dry season, despite the low density of mosquito populations.ConclusionThese results demonstrate that the intensity of malaria transmission is extremely high in Gbêkê region, especially during the rainy season. The study highlights the risk factors of transmission that could negatively impact current interventions that target indoor control, as well as the urgent need for additional vector control tools to target the population of malaria vectors in Gbêkê region and reduce the burden of the disease.

Proof-of-concept study for a long-acting formulation of ivermectin injected in cattle as a complementary malaria vector control tool

BackgroundDomesticated animals play a role in maintaining residual transmission of Plasmodium parasites of humans, by offering alternative blood meal sources for malaria vectors to survive on. However, the blood of animals treated with veterinary formulations of the anti-helminthic drug ivermectin can have an insecticidal effect on adult malaria vector mosquitoes. This study therefore assessed the effects of treating cattle with long-acting injectable formulations of ivermectin on the survival of an important malaria vector species, to determine whether it has potential as a complementary vector control measure.MethodsEight head of a local breed of cattle were randomly assigned to either one of two treatment arms (2 × 2 cattle injected with one of two long-acting formulations of ivermectin with the BEPO® technology at the therapeutic dose of 1.2 mg/kg), or one of two control arms (2 × 2 cattle injected with the vehicles of the formulations). The lethality of the formulations was evaluated on 3–5-day-old Anopheles coluzzii mosquitoes through direct skin-feeding assays, from 1 to 210 days after treatment. The efficacy of each formulation was evaluated and compared using Cox proportional hazards survival models, Kaplan–Meier survival estimates, and log-logistic regression on cumulative mortality.ResultsBoth formulations released mosquitocidal concentrations of ivermectin until 210 days post-treatment (hazard ratio > 1). The treatments significantly reduced mosquito survival, with average median survival time of 4–5 days post-feeding. The lethal concentrations to kill 50% of the Anopheles (LC50) before they became infectious (10 days after an infectious blood meal) were maintained for 210 days post-injection for both formulations.ConclusionsThis long-lasting formulation of ivermectin injected in cattle could complement insecticide-treated nets by suppressing field populations of zoophagic mosquitoes that are responsible, at least in part, for residual malaria transmission. The impact of this approach will of course depend on the field epidemiological context. Complementary studies will be necessary to characterize ivermectin withdrawal times and potential environmental toxicity.Graphical

GAMETOCYTE DYNAMICS AND THE EFFECTS OF AQUEOUS AND ETHANOLIC LEAF EXTRACTS OF Lophira Lanceolata IN MICE INFECTED WITH Plasmodium Bergei

Resistance of human malaria parasites to existing chemotherapeutic drugs remains a global challenge to malaria control. This study was an evaluation of the gametocyte dynamics and the potential roles of aqueous and ethanolic leaf extracts of Lophira lanceolata in the transmission of Plasmodium parasites using mice experimentally infected with P.berghei as a model. A total of 192 experimental mice divided into 15 groups in a randomized block design and replicated four times with four mice in each group were used for this study. Thirty-six (36) mice were used for acute toxicity test, 32 mice each for curative antiplasmodial assay, prophylactic assay and gametocyte evaluation, and analyses. Experimental mice were inoculated intraperitoneally with standard inoculum of 1 x 107P.berghei parasitized red blood cells on first day (DO). Body weights of mice were taken using sensitive digital weighing balance. Blood sample was collected by cardiac puncture using sterile needle and 5ml syringe and preserved in ethylene diaminetetraacetic acid (EDTA) bottle. Haematological components were determined using an autohaematology analyzer SYSMEX KX21. Data analysis was done using student’s t-test and one way analysis of variance with multiple comparison tests. Phytochemical screening revealed the presence of phenols, terpenoids, tannins, saponins, alkaloids, flavonoids, steroids, oxalates and cardiac glycosides. The flavonoids had the largest concentrations of 388.24mg/ml, and 350.00mg/ml in ethanolic and aqueous extracts respectively. LD50 was found to be > 5000mg/kg body weight in both extracts. At > 100mg/kg body weight, infected treated mice experienced body weight increases while infected untreated mice experienced decreases in mean body weight from 23.33g to 20.08g (mean 10% weight loss). Aqueous and ethanolic leaf extracts produced variations in number of gametocyte from mice infected with P.berghei. On days 7, 14, 21, and 28, the mean gametocytes of the parasite in the control group were 18, 21, 22, and 20 respectively which were significantly (p < 0.05) higher compared with the mean gametocytes in the groups of mice treated with aqueous extract, ethanolic extract and chloroquine drugs. The dose level of 10mg/kg body weight of aqueous extract produced the mean gametocyte counts of 10, 10, 8 and 6 on days 7, 14, 21 and 28 respectively which were significantly (p < 0.05) lower than the mean gametocyte counts of the control

Mosquito aquatic habitat modification and manipulation interventions to control malaria.

Mosquito aquatic habitat modification and manipulation interventions to control malaria.

Safety, tolerability, and Plasmodium falciparum transmission-reducing activity of monoclonal antibody TB31F: a single-centre, open-label, first-in-human, dose-escalation, phase 1 trial in healthy malaria-naive adults

Malaria elimination requires interruption of the highly efficient transmission of Plasmodium parasites by mosquitoes. TB31F is a humanised monoclonal antibody that binds the gamete surface protein Pfs48/45 and inhibits fertilisation, thereby preventing further parasite development in the mosquito midgut and onward transmission. We aimed to evaluate the safety and efficacy of TB31F in malaria-naive participants. In this open-label, first-in-human, dose-escalation, phase 1 clinical trial, healthy, malaria-naive, adult participants were administered a single intravenous dose of 0·1, 1, 3, or 10 mg/kg TB31F or a subcutaneous dose of 100 mg TB31F, and monitored until day 84 after administration at a single centre in the Netherlands. The primary outcome was the frequency and magnitude of adverse events. Additionally, TB31F serum concentrations were measured by ELISA. Transmission-reducing activity (TRA) of participant sera was assessed by standard membrane feeding assays with Anopheles stephensi mosquitoes and cultured Plasmodium falciparum gametocytes. The trial is registered with Clinicaltrials.gov, NCT04238689. Between Feb 17 and Dec 10, 2020, 25 participants were enrolled and sequentially assigned to each dose (n=5 per group). No serious or severe adverse events occurred. In total, 33 grade 1 and six grade 2 related adverse events occurred in 20 (80%) of 25 participants across all groups. Serum of all participants administered 1 mg/kg, 3 mg/kg, or 10 mg/kg TB31F intravenously had more than 80% TRA for 28 days or more, 56 days or more, and 84 days or more, respectively. The TB31F serum concentration reaching 80% TRA was 2·1 μg/mL (95% CI 1·9-2·3). Extrapolating the duration of TRA from antibody kinetics suggests more than 80% TRA is maintained for 160 days (95% CI 136-193) following a single intravenous 10 mg/kg dose. TB31F is a well tolerated and highly potent monoclonal antibody capable of completely blocking transmission of P falciparum parasites from humans to mosquitoes. In areas of seasonal transmission, a single dose might cover an entire malaria season. PATH's Malaria Vaccine Initiative.

Transgenic Anopheles mosquitoes expressing human PAI-1 impair malaria transmission

In mammals, the serine protease plasmin degrades extracellular proteins during blood clot removal, tissue remodeling, and cell migration. The zymogen plasminogen is activated into plasmin by two serine proteases: tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), a process regulated by plasminogen activator inhibitor 1 (PAI-1), a serine protease inhibitor that specifically inhibits tPA and uPA. Plasmodium gametes and sporozoites use tPA and uPA to activate plasminogen and parasite-bound plasmin degrades extracellular matrices, facilitating parasite motility in the mosquito and the mammalian host. Furthermore, inhibition of plasminogen activation by PAI-1 strongly blocks infection in both hosts. To block parasite utilization of plasmin, we engineered Anopheles stephensi transgenic mosquitoes constitutively secreting human PAI-1 (huPAI-1) in the midgut lumen, in the saliva, or both. Mosquitoes expressing huPAI-1 strongly reduced rodent and human Plasmodium parasite transmission to mosquitoes, showing that co-opting plasmin for mosquito infection is a conserved mechanism among Plasmodium species. huPAI-1 expression in saliva induced salivary gland deformation which affects sporozoite invasion and P. berghei transmission to mice, resulting in significant levels of protection from malaria. Targeting the interaction of malaria parasites with the fibrinolytic system using genetically engineered mosquitoes could be developed as an intervention to control malaria transmission.

Aqueous and ethanolic leaf extracts leaf extracts of Lophira Lanceolata properties effect in mice infected with Plasmodium berghei

This study was to determine the effects of Lophira lanceolata leaf extracts on haematological, biochemical, and histopathological parameters of the mice in the transmission of Plasmodium parasites using mice infected with P.berghei as a model. A total of 196 experimental mice divided into 15 groups in a randomized block design and replicated four times with four mice in each group were used for this study. Thirty six (36) mice were used for acute toxicity test, 50 each for haematological, biochemical, and histopathological analyses. Experimental mice were inoculated intraperitoneally with standard inoculum of 1 x 107 P.berghei parasitized red blood cells on first day (DO). Data analysis was done using student’s t-test and one way analysis of variance with multiple comparison tests. Aqueous leaf extract exerted significant (p < 0.05) non-dose dependent reduction in parasitaemia level with chemosuppression of 48.79%, 24.26%, 29.38% and 80.32% at 10, 100, 200 mg/kg body weight and 5mg/kg body weight chloroquine treated groups respectively. Dose level of 10, 100, 200 mg/ kg body weight of both aqueous and ethanolic leaf extract produced significant increases in aspartate amino transferase, alanine amino transferase, total bilirubin, cholesterol, triglycerides and urea profiles of infected treated mice compared with the control. At 200mg /kg body weight of aqueous extract there was a significant decrease (p < 0.05) in weight of liver and kidney organs in the infected treated mice compared with the control. The results of histopathological examinations of the liver organs of the mice were characterized by tissue stromal proliferation, enlarged hepatocytes and disorganized sinusoids and lamina of hepatic cells.The results of histopathological examination of kidneys showed no histopathological changes.The aqueous and ethanolic leaf extracts of Lophira lanceolata plant showed significant antiplasmodium activities comparable to chloroquine drugs.The leaf extracts of Lophira lanceolata plant had gametocytocidal action on P. berghei. The results of the haematological, biochemical and histopathological examinations indicated that caution should be exercised while taking the plant extract as an antimalarial agent.

Residual Malaria: Limitations of Current Vector Control Strategies to Eliminate Transmission in Residual Foci

The transmission of Plasmodium parasites in residual foci is currently a major roadblock for malaria elimination. Human activities and behavior, along with outdoor biting mosquitoes with opportunistic feeding preferences are the main causes of the inefficacy of the main vector control interventions, long lasting insecticide-impregnated nets and insecticide residual spraying. Several strategies to abate or repel outdoor biting mosquito vectors are currently being researched, but the impact of insecticide resistance on the efficacy of these and current indoor-applied insecticides requires further assessment. Understanding the human, ecological and vector factors, determining transmission in residual foci is necessary for the design and implementation of novel control strategies. Vector control alone is insufficient without adequate epidemiological surveillance and prompt treatment of malaria cases, the participation of endemic communities in prevention and control is required. In addition, malaria control programs should optimize their structure and organization, and their coordination with other government sectors.

Natural Products: A Potential Source of Malaria Transmission Blocking Drugs?

The ability to block human-to-mosquito and mosquito-to-human transmission of Plasmodium parasites is fundamental to accomplish the ambitious goal of malaria elimination. The WHO currently recommends only primaquine as a transmission-blocking drug but its use is severely restricted by toxicity in some populations. New, safe and clinically effective transmission-blocking drugs therefore need to be discovered. While natural products have been extensively investigated for the development of chemotherapeutic antimalarial agents, their potential use as transmission-blocking drugs is comparatively poorly explored. Here, we provide a comprehensive summary of the activities of natural products (and their derivatives) of plant and microbial origins against sexual stages of Plasmodium parasites and the Anopheles mosquito vector. We identify the prevailing challenges and opportunities and suggest how these can be mitigated and/or exploited in an endeavor to expedite transmission-blocking drug discovery efforts from natural products.

Polarization of MTIP is a signature of gliding locomotion in Plasmodium ookinetes and sporozoites

Gliding motility and cell invasion are essential for the successful transmission of Plasmodium parasites. These processes rely on an acto-myosin motor located underneath the parasite plasma membrane. The Myosin A-tail interacting protein (MTIP) connects the class XIV myosin A (MyoA) to the gliding-associated proteins and is essential for assembly of the motor at the inner membrane complex. Here, we assessed the subcellular localization of MTIP in Plasmodium berghei motile stages from wild-type parasites and mutants that lack MyoA or the small heat shock protein 20 (HSP20). We demonstrate that MTIP is recruited to the apical end of motile ookinetes independently of the presence of MyoA. We also show that infective sporozoites displayed a polarized MTIP distribution during gliding, and that this distribution was abrogated in mutant parasites with an aberrant locomotion.

Plasmodium sexual differentiation: how to make a female.

Sexual development is integral to the transmission of Plasmodium parasites between vertebrates and mosquitos. Recent years have seen great advances in understanding the gene expression that underlies commitment of asexual parasites to differentiate into sexual gametocyte stages, then how they mature and form gametes once inside a mosquito. Less well understood is how parasites differentially control development to become males or females. Plasmodium parasites are haploid at the time of sexual differentiation, but a clonal haploid line can produce both male and female gametocytes, so they presumably lack the sex-determining alleles present in some other eukaryotes. Though the molecular switch to initiate male or female development remains hidden, recent studies reveal regulatory proteins needed for the sex-specific maturation of male and female gametocytes. Yuda and collaborators report the characterization of a transcription factor necessary for female gametocyte maturation. With renewed attention on malaria elimination, sex has been an increasing focus because transmission-blocking strategies are likely to be an important component of elimination efforts.

Prevalence of human and non-human primate Plasmodium parasites in anopheline mosquitoes: a cross-sectional epidemiological study in Southern Vietnam

BackgroundHuman malaria is a major threat in rural communities of central Vietnam. Anopheles dirus and Anopheles minimus species are critical malaria vectors in Vietnam, which transmit Plasmodium parasites. However, the entomological aspects of malaria transmission in some of the central provinces of Vietnam remain unexplored. Hence, a cross-sectional entomological survey was carried out to identify the malaria vector species and the transmission of Plasmodium parasites in seven endemic provinces of Vietnam.MethodsMosquitoes were collected from seven provinces, Gia Lai, Khanh Hoa, Phu Yen, Ninh Thuan, Binh Thuan, Dong Nai, and Binh Phuoc. The collection was conducted for four to eight consecutive nights using three established methods, indoor and outdoor human landing catches and light trap method. Nested-PCR analysis was performed to detect the Plasmodium species in the separated thorax and the abdomen of the individual mosquitoes.ResultsA total of 2278 mosquitoes belonging to one of the four species of anopheline mosquitoes, An. dirus, An. maculatus, An. aconitus, and An. minimus were collected. Among the collected mosquitoes, 1398 were analysed using nested-PCR, of which, 40 mosquitoes were positive for Plasmodium parasites. Most of these parasites were detected in the samples from the thorax region, followed by the abdominal portion. The parasites were detected in both the thorax and abdomen of An. dirus. Seven species of Plasmodium parasites were detected during the analysis, of which, Plasmodium inui was the most common species, followed by Plasmodium falciparum, Plasmodium vivax, Plasmodium cynomolgi, Plasmodium coatneyi, Plasmodium knowlesi, and Plasmodium fieldi. Out of the 49 positive samples, 12 showed mixed infections. Co-infection of P. inui with human and other non-human primate Plasmodium species was common.ConclusionsThis study demonstrated the presence of human and non-human primate Plasmodium infection in An. dirus, a predominant malarial vector. Further, we showed that An. maculatus and An. minimus species also take part in malarial transmission. This might potentially lead to an alarming situation conducive for the emergence of novel zoonotic malaria.

Analysis of polymorphisms in the circumsporozoite protein gene of Plasmodium vivax isolates from Henan Province, China

BackgroundPlasmodium vivax malaria has historically been a major source of disease in Henan, China. In the 1970s, the morbidity of malaria was highest in the country. With support from the government and the efforts of healthcare personnel, the reported malaria cases have declined dramatically and a national elimination programme was launched in 2010. To achieve the goal, it is essential to study the diversity of autochthonous malaria and transmission of Plasmodium parasites, which will provide baseline data for disease control and management.MethodsThirty-two P. vivax isolates from Henan province were collected from 2008 to 2011, and circumsporozoite protein (csp) genes were analysed to estimate the genetic diversity of this parasite.ResultsThe assessment of csp sequences indicated that all the isolates were the VK210 type, however, none of them was identical to the VK210 strain. The sequences displayed variations in the central region, and eight sub-types were observed. Among the sub-types, HN7 was the most prevalent (37.5%), followed by HN3 (34.4%). A total of 653 repeat units were discovered in 32 Henan isolates. Nucleotide sequences were grouped in 13 unique repeat nucleotide sequence allotypes that coded for 7 different repeated amino acid allotypes. B (GNGAGGQAA) and D (GDRAAGQPA) were more frequent based on the results; they represented 53.9% (352/653) of the total. In comparison to the basic repeat units of VK210, more than 75% of the central repeat units had at least one non-synonymous nucleotide change.ConclusionsRecent P. vivax populations in Henan province showed some degree of genetic diversity in csp, with 8 sub-types among 32 samples. Meantime, the results also suggested its relative conserved parasite populations. This could provide interesting baseline data that allow identifying whether potential new cases differ from the parasites already circulating in the area.

Unforeseen pathologies caused by malaria.

Individuals from malaria-endemic regions often acquire partial immunity after multiple repeated infections throughout their lives. This partial immunity prevents them from developing severe complications and they often remain asymptomatic with a persistent, low parasite density in the blood, and therefore the necessity for treatment is neglected. These patients with chronic, asymptomatic malaria serve as a reservoir for Plasmodium parasite transmission, becoming a major obstacle for eradication efforts. The constant exposure to malaria infection may have benefits in the short term by conferring protection from acute, severe malaria; however, it may cause substantially more harm in the long term. Rather than the parasite burden itself, the complications induced by the dysregulated immune responses and the tissue damage done by the parasites and their products can cause chronic and irreversible suffering. Furthermore, the complete clearance of parasites in the body may not lead to complete recovery from the disease as complications can still persist. The fact that there are chronic pathologies caused by malaria that mostly remain obscure and have the potential to cause a serious burden has recently been gaining attention. Here, we present and discuss the evidence of unforeseen pathologies and the risks associated with malaria.

Larvivorous fish for preventing malaria transmission.

Larvivorous fish for preventing malaria transmission.

Administration of ivermectin to peridomestic cattle: a promising approach to target the residual transmission of human malaria.

BackgroundThe success of current control tools in combatting malaria vectors is well established. However, sustained residual transmission of Plasmodium parasites persists. Mass drug administration (MDA) to humans of the endectocide ivermectin for vector control is receiving increasing attention. However, vectors feeding upon animals escape this promising approach. Zoophagy of mosquitoes sustains both the vector population and endemic population of vector-borne pathogens. Therefore, only a strategy that will combine ivermectin MDAs targeted at humans and their peridomestic animals could be successful at controlling residual malaria transmission.MethodsBurkinabé cattle have been treated with injectable therapeutic dose of ivermectin (0.2 mg/kg of body weight) to render blood meals toxic to field representative populations of Anopheles coluzzii carrying the kdr mutation. Direct skin-feeding assays were performed from 2 to 28 days after injection (DAI) and mosquitoes were followed for their survival, ability to become gravid and fecundity. Membrane feeding assays were further performed to test if an ivermectin blood meal taken at 28 DAI impacts gametocyte establishment and development in females fed with infectious blood.ResultsThe mosquitocidal effect of ivermectin is complete for 2 weeks after injection, whether 12 days cumulative mortalities were of 75 and 45 % the third and fourth weeks, respectively. The third week, a second ivermectin blood meal at sub-lethal concentrations further increased mortality to 100 %. Sub-lethal concentrations of ivermectin also significantly decreased egg production by surviving females, increasing further the detrimental effect of the drug on vector densities. Although females fitness was impaired by sub-lethal ivermectin blood meals, these did not diminish nor increase their susceptibility to infection.ConclusionThis study demonstrates the potential of integrated MDA of ivermectin to both human and peridomestic cattle to target vector reservoirs of residual malaria transmission. Such integration lies in ‘One-Health’ efforts being implemented around the globe, and would be especially relevant in rural communities in Africa where humans are also at risk of common zoonotic diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-1001-z) contains supplementary material, which is available to authorized users.

Morphologic and molecular study of hemoparasites in wild corvids and evidence of sequence identity with Plasmodium DNA detected in captive black-footed penguins (Spheniscus demersus).

A morphologic and molecular epidemiologic investigation was conducted on a captive African black-footed penguin (Spheniscus demersus) colony with a history of Plasmodium infections at La Palmyre Zoo (France). Each penguin received 12.5 mg of pyrimethamine twice a week as a prophylaxis every year from April to November. Although Plasmodium parasites were not detected in blood smears and tissues collected from the penguins, various blood parasites were recorded in blood smears from wild Eurasian magpies (Pica pica) and carrion crows (Corvus corone) sampled at the same time in the study area. These parasites consisted of several Plasmodium spp. (P. lenoblei, P. dorsti, P bioccai, P. relictum, P. dherteae, P. beaucournui, P. maior, P. tranieri, and P. snounoui), Parahaemoproteus spp., Trypanosoma spp., and Leucocytozoon spp. On the other hand, nested polymerase chain reaction enabled detection of Plasmodium DNA in 28/44 (64%) penguins, 15/25 (60%) magpies, and 4/9 (44%) crows. Sequencing and phylogenetic analyses indicated that the parasite DNA amplified from the penguins, magpies, and crows were similar. Magpies and crows could therefore act as a reservoir for penguin Plasmodium infections, which may be more prevalent than previously thought. Morphologic characterization of the Plasmodium spp. detected in the penguins, as well as further biological and epidemiologic studies, are needed to fully understand the transmission of Plasmodium parasites to captive penguins.

Modeling Within-Host Effects of Drugs on Plasmodium falciparum Transmission and Prospects for Malaria Elimination

Achieving a theoretical foundation for malaria elimination will require a detailed understanding of the quantitative relationships between patient treatment-seeking behavior, treatment coverage, and the effects of curative therapies that also block Plasmodium parasite transmission to mosquito vectors. Here, we report a mechanistic, within-host mathematical model that uses pharmacokinetic (PK) and pharmacodynamic (PD) data to simulate the effects of artemisinin-based combination therapies (ACTs) on Plasmodium falciparum transmission. To contextualize this model, we created a set of global maps of the fold reductions that would be necessary to reduce the malaria RC (i.e. its basic reproductive number under control) to below 1 and thus interrupt transmission. This modeling was applied to low-transmission settings, defined as having a R0<10 based on 2010 data. Our modeling predicts that treating 93–98% of symptomatic infections with an ACT within five days of fever onset would interrupt malaria transmission for ∼91% of the at-risk population of Southeast Asia and ∼74% of the global at-risk population, and lead these populations towards malaria elimination. This level of treatment coverage corresponds to an estimated 81–85% of all infected individuals in these settings. At this coverage level with ACTs, the addition of the gametocytocidal agent primaquine affords no major gains in transmission reduction. Indeed, we estimate that it would require switching ∼180 people from ACTs to ACTs plus primaquine to achieve the same transmission reduction as switching a single individual from untreated to treated with ACTs. Our model thus predicts that the addition of gametocytocidal drugs to treatment regimens provides very small population-wide benefits and that the focus of control efforts in Southeast Asia should be on increasing prompt ACT coverage. Prospects for elimination in much of Sub-Saharan Africa appear far less favorable currently, due to high rates of infection and less frequent and less rapid treatment.