scholarly journals Non-human primate and human malaria: past, present and future

Author(s):  
Spinello Antinori ◽  
Cecilia Bonazzetti ◽  
Andrea Giacomelli ◽  
Mario Corbellino ◽  
Massimo Galli ◽  
...  

Abstract Background Studies of the malaria parasites infecting various non-human primates (NHPs) have increased our understanding of the origin, biology and pathogenesis of human Plasmodium parasites. This review considers the major discoveries concerning NHP malaria parasites, highlights their relationships with human malaria and considers the impact that this may have on attempts to eradicate the disease. Results The first description of NHP malaria parasites dates back to the early 20th century. Subsequently, experimental and fortuitous findings indicating that some NHP malaria parasites can be transmitted to humans have raised concerns about the possible impact of a zoonotic malaria reservoir on efforts to control human malaria. Advances in molecular techniques over the last 15 years have contributed greatly to our knowledge of the existence and geographical distribution of numerous Plasmodium species infecting NHPs, and extended our understanding of their close phylogenetic relationships with human malaria parasites. The clinical application of such techniques has also made it possible to document ongoing spillovers of NHP malaria parasites (Plasmodium knowlesi, P. cynomolgi, P. simium, P. brasilianum) in humans living in or near the forests of Asia and South America, thus confirming that zoonotic malaria can undermine efforts to eradicate human malaria. Conclusions Increasing molecular research supports the prophetic intuition of the pioneers of modern malariology who saw zoonotic malaria as a potential obstacle to the full success of malaria eradication programmes. It is, therefore, important to continue surveillance and research based on one-health approaches in order to improve our understanding of the complex interactions between NHPs, mosquito vectors and humans during a period of ongoing changes in the climate and the use of land, monitor the evolution of zoonotic malaria, identify the populations most at risk and implement appropriate preventive strategies.

2017 ◽  
Author(s):  
Mitsuhiro Odaka ◽  
Amen Sassy ◽  
Shymmaa Khatab ◽  
Linh Tran ◽  
Khaled Ismaeil ◽  
...  

Human Plasmodium species have a sex specific process in the life cycle namely gametocytogenesis or gametogenesis. Gametocytes production and subsequent gametes zygosis are critical for malaria parasites to link to mosquito stage and to merge to sexual reproduction. Here, we aimed at the identification of genes related to gametocytogenesis or gametogenesis in human malaria using systematic review, meta-synthesis and homology search. Based on our search terms, we conducted a systematic search of published data in nine databases resulting in 96 finally included papers with a total of 255 genes from apicomplexan species. We found more papers involved in Plasmodium than we had expected, which reflects that the extensive amount of research on Plasmodium genes have been examined. Subsequently we searched sequence homology between FASTA sequences of apicomplexan sex specific genes other than human malaria parasites and those of human malaria parasites genome on PlasmoDB. We focused on eight candidate genes of Plasmodium falciparum (PF). Finally we predicted that PRPF6, SMC1 and SMC2 can be the especially promising candidate genes.


2017 ◽  
Vol 7 (8) ◽  
pp. 680-685 ◽  
Author(s):  
Thu Zar Han ◽  
Kay Thwe Han ◽  
Kyin Hla Aye ◽  
Thaung Hlaing ◽  
Kyaw Zin Thant ◽  
...  

2020 ◽  
Author(s):  
Wirasak Fungfuang ◽  
Chanya Udom ◽  
Daraka Tongthainan ◽  
Khamisah Abdul Kadir ◽  
Balbir Singh

Abstract Background:Certain species of macaques are natural hosts ofPlasmodium knowlesi and P. cynomolgi, which can both cause malaria in humans, and P. inui, which can be experimentally transmitted to humans. A significant number of zoonotic malaria cases have been reported in humans throughout Southeast Asia, including Thailand. There have been only two studies undertaken in Thailand to identify malaria parasites in non-human primates in 6 provinces. The objective of this study was to determine the prevalence of P. knowlesi, P. coatneyi, P. cynomolgi, P. inui and P. fieldiin non-human primates from 4 new locations in Thailand. Methods:A total of 93 blood samples from Macaca fascicularis, M. leonina and M. arctoides were collected from four locations in Thailand: 32 were captive M. fascicularisfrom Chachoengsao Province (CHA), 4 were wild M. fascicularis from Ranong Province (RAN), 32 were wildM. arctoidesfromPrachuap Kiri Khan Province (PRA), and 25 were wild M. leoninafrom Nakornratchasima Province (NAK). DNA was extracted from these samples and analysed by nested PCR assays to detect Plasmodium, and subsequently to detectP. knowlesi, P. coatneyi, P. cynomolgi, P. inui and P. fieldi.Results:Twenty-seven of the 93 (29%) samples were Plasmodium-positive by nested PCR assays. Among wild macaques, all 4 M. fascicularis at RAN were infected with malaria parasites followed by 50% of 32 M. arctoides at PRA and 20% of 25 M. leonina at NAK. Only 2 (6.3%) of the 32 captive M. fascicularisat CHA were malaria-positive. All 5 species of Plasmodium were detected and 16 (59.3%) of the 27 macaques had single infections, 9had double and 2 had triple infections.The composition of Plasmodium species in macaques at each sampling site was different. Macaca arctoides from PRA were infected with P. knowlesi, P. coatneyi, P. cynomolgi, P. inui and P. fieldi. Conclusions:The prevalence and species of Plasmodiumvaried among the wild and captive macaques, and betweenmacaques at 4 sampling sites in Thailand. Macaca arctoidesis a new natural host for P. knowlesi, P. inui,P. coatneyi and P. fieldi.


2020 ◽  
Author(s):  
Amber E. Trujillo ◽  
Christina M. Bergey

AbstractMalaria is infamous for the massive toll it exacts on human life and health. In the face of this intense selection, many human populations have evolved mechanisms that confer some resistance to the disease, such as sickle-cell hemoglobin or the Duffy null blood group. Less understood are adaptations in other vertebrate hosts, many of which have a longer history of co-evolution with malaria parasites. By comparing malaria resistance adaptations across host species, we can gain fundamental insight into host-parasite co-evolution. In particular, understanding the mechanisms by which non-human primate immune systems combat malaria may be fruitful in uncovering transferable therapeutic targets for humans. However, most research on primate response to malaria has focused on a single or few loci, typically in experimentally-infected captive primates. Here, we report the first transcriptomic study of a wild primate response to a malaria-like parasite, investigating gene expression response of red colobus monkeys (Piliocolobus tephrosceles) to natural infection with the malaria-like parasite, Hepatocystis. We identified colobus genes with expression strongly correlated with parasitemia, including many implicated in human malaria and suggestive of common genetic architecture of disease response. For instance, the expression of ACKR1 (alias DARC) gene, previously linked to resistance in humans, was found to be positively correlated with parasitemia. Other similarities to human parasite response include induction of changes in immune cell type composition and, potentially, increased extramedullary hematopoiesis and altered biosynthesis of neutral lipids. Our results illustrate the utility of comparative immunogenetic investigation of malaria response in primates. Such inter-specific comparisons of transcriptional response to pathogens afford a unique opportunity to compare and contrast the adaptive genetic architecture of disease resistance, which may lead to the identification of novel intervention targets to improve human health.Author SummaryThe co-evolutionary arms race between humans and malaria parasites has been ongoing for millennia. Fully understanding the evolved human response to malaria is impossible without comparative study of parasites in our non-human primate relatives. Though laboratory primates are fruitful models, the complexity of wild primates infected in a natural transmission system may be a more suitable comparison for contextualizing malaria infections in human patients. Here, we investigate the genetic mechanisms underlying the immune response to Hepatocystis, a close relative of human-infective malaria, in a population of wild Ugandan red colobus monkeys. We find that the genes involved have considerable overlap with those active in human malaria patients. Like Plasmodium, Hepatocystis induces changes in blood cell type and may cause the host to produce blood components outside of the bone marrow or alter metabolism related to the production of lipids. Our work helps to identify the genetic mechanisms underlying the arms race between primates and malaria parasites, providing fundamental evolutionary insight. Such comparative work on the interaction between wild non-human primates and malaria parasites can identify ways in which primates have evolved resistance to malaria parasites, and further investigation of such implicated genes may lead to novel potential therapeutic and vaccine targets.


2020 ◽  
Author(s):  
Joshua Ang Xin De ◽  
Khamisah Abdul Kadir ◽  
Dayang Shuaisah Awang Mohamad ◽  
Asmad Matusop ◽  
Paul Cliff Simon Divis ◽  
...  

Abstract Background: The vectors for Plasmodium knowlesi, a significant cause of human malaria in Southeast Asia, identified previously in nature all belong to the Anopheles Leucosphyrus Group. Only one study has been previously undertaken in Sarawak, Malaysian Borneo, to identify vectors of P. knowlesi , where Anopheles latens was incriminated as the vector in Kapit, central Sarawak. A study was therefore undertaken to identify malaria vectors in a different location in Sarawak. Methods: Mosquitoes found landing on humans and resting on leaves over a 5-day period at two sites in the Lawas District of northern Sarawak were collected and identified. DNA samples extracted from salivary glands of Anopheles mosquitoes were subjected to nested PCR malaria-detection assays. The small sub-unit ribosomal RNA (SSUrRNA) genes of Plasmodium , and the internal transcribed spacer 2 (ITSII) and mitochondrial cytochrome c oxidase subunit 1 (COI) sequences of the mosquitoes were derived from the Plasmodium -positive samples for phylogenetic analyses. Results: A total of 65 anophelines and 127 culicines were collected. By PCR, six An. balabacensis and five An. barbirostris Clade VI were found to have single P. knowlesi infecions while three other An. balabacensis had either single, double or triple infections with P. inui, P. fieldi, P. cynomolgi and P. knowlesi . Phylogenetic analyses of the Plasmodium SSUrRNA genes confirmed 3 An. barbirostris Clade VI and 3 An. balabacensis with single P. knowlesi infections, while 3 other An. balabacensis had two or more Plasmodium species of P. inui, P. knowlesi, P. cynomolgi and possibly novel species of Plasmodium . Phylogenies inferred from the ITSII and COI sequences of An. balabacensis and An. barbirostris Clade VI indicate that the former is genetically indistinguishable from An. balabacensis in Borneo while the latter is a novel sibling species belonging to the Anopheles Barbirostris Subgroup. Conclusions: New vectors for P. knowlesi in Sarawak were identified, including An. barbirostris Clade VI , which is a species that does not belong to the Anopheles Leucosphyrus Group.


2020 ◽  
Author(s):  
Mohd 'Ammar Ihsan Ahmad Zamzuri ◽  
Mohd Rohaizat Hassan ◽  
Rozita Hod

Abstract Background Plasmodium knowlesi infection has significant morbidity and mortality impact in Malaysia. This zoonotic malaria parasite is naturally transmissible from macaque to humans in the presence of a competent vector. Human encroachment towards the habitat of macaque has further increased the risk. Stratifying the potential risk of transmission based on the burden of parasite among macaque in a particular area can be the first step for public health intervention. Thus, the study aimed to estimate the prevalence of Plasmodium knowlesi parasite among macaque in Negeri Sembilan and determine its associated factors. METHODS This is a cross-sectional study using a non-probabilistic sampling technique. A total of 212 blood samples from macaques in Negeri Sembilan were collected from seven districts. The Plasmodium spp. infecting the macaques were identified using Real-Time PCR assays on DNA extracted from these blood samples. Statistical tests were done to examine the factors associated with Plasmodium knowlesi infection in the macaque population. RESULT The overall prevalence of Plasmodium knowlesi among macaque in Negeri Sembilan state was 36.3%. Both long-tailed macaque and short-tailed macaque harboured the parasite within them. Co-infection with several malaria parasites were seen in 35.5% of Plasmodium spp positive results. The only significant associated factors in the prevalence of Plasmodium knowlesi were the type of locality (rural vs. urban) and the districts where the macaques were trapped. CONCLUSION The prevalence of Plasmodium knowlesi infection among macaques varied between districts in Negeri Sembilan. The presence of zoonotic malaria parasites among the population of macaque that live in close proximity with the community possesses a potential risk of transmission. Therefore, robust public health advocacy targeting high-risk areas is deemed necessary.


mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Hyeogsun Kwon ◽  
Maria L. Simões ◽  
Rebekah A. Reynolds ◽  
George Dimopoulos ◽  
Ryan C. Smith

ABSTRACT Mosquitoes may feed multiple times during their life span in addition to those times needed to acquire and transmit malaria. To determine the impact of subsequent blood feeding on parasite development in Anopheles gambiae, we examined Plasmodium parasite infection with or without an additional noninfected blood meal. We found that an additional blood meal significantly reduced Plasmodium berghei immature oocyst numbers, yet had no effect on the human parasite Plasmodium falciparum. These observations were reproduced when mosquitoes were fed an artificial protein meal, suggesting that parasite losses are independent of blood ingestion. We found that feeding with either a blood or protein meal compromises midgut basal lamina integrity as a result of the physical distention of the midgut, enabling the recognition and lysis of immature P. berghei oocysts by mosquito complement. Moreover, we demonstrate that additional feeding promotes P. falciparum oocyst growth, suggesting that human malaria parasites exploit host resources provided with blood feeding to accelerate their growth. This is in contrast to experiments with P. berghei, where the size of surviving oocysts is independent of an additional blood meal. Together, these data demonstrate distinct differences in Plasmodium species in evading immune detection and utilizing host resources at the oocyst stage, representing an additional, yet unexplored component of vectorial capacity that has important implications for the transmission of malaria. IMPORTANCE Mosquitoes must blood feed multiple times to acquire and transmit malaria. However, the impact of an additional mosquito blood meal following malaria parasite infection has not been closely examined. Here, we demonstrate that additional feeding affects mosquito vector competence; namely, additional feeding significantly limits Plasmodium berghei infection, yet has no effect on infection of the human parasite P. falciparum. Our experiments support that these killing responses are mediated by the physical distension of the midgut and by temporary damage to the midgut basal lamina that exposes immature P. berghei oocysts to mosquito complement, while human malaria parasites are able to evade these killing mechanisms. In addition, we provide evidence that additional feeding promotes P. falciparum oocyst growth. This is in contrast to P. berghei, where oocyst size is independent of an additional blood meal. This suggests that human malaria parasites are able to exploit host resources provided by an additional feeding to accelerate their growth. In summary, our data highlight distinct differences in malaria parasite species in evading immune recognition and adapting to mosquito blood feeding. These observations have important, yet previously unexplored, implications for the impact of multiple blood meals on the transmission of malaria.


2019 ◽  
Vol 70 (3) ◽  
pp. 361-367 ◽  
Author(s):  
Daniel J Cooper ◽  
Giri S Rajahram ◽  
Timothy William ◽  
Jenarun Jelip ◽  
Rashidah Mohammad ◽  
...  

Abstract Background Malaysia aims to eliminate malaria by 2020. However, while cases of Plasmodium falciparum and Plasmodium vivax have decreased substantially, the incidence of zoonotic malaria from Plasmodium knowlesi continues to increase, presenting a major challenge to regional malaria control efforts. Here we report incidence of all Plasmodium species in Sabah, including zoonotic P. knowlesi, during 2015–2017. Methods Microscopy-based malaria notification data and polymerase chain reaction (PCR) results were obtained from the Sabah Department of Health and State Public Health Laboratory, respectively, from January 2015 to December 2017. From January 2016 this was complemented by a statewide prospective hospital surveillance study. Databases were matched, and species was determined by PCR, or microscopy if PCR was not available. Results A total of 3867 malaria cases were recorded between 2015 and 2017, with PCR performed in 93%. Using PCR results, and microscopy if PCR was unavailable, P. knowlesi accounted for 817 (80%), 677 (88%), and 2030 (98%) malaria cases in 2015, 2016, and 2017, respectively. P. falciparum accounted for 110 (11%), 45 (6%), and 23 (1%) cases and P. vivax accounted for 61 (6%), 17 (2%), and 8 (0.4%) cases, respectively. Of those with P. knowlesi, the median age was 35 (interquartile range: 24–47) years, and 85% were male. Conclusions Malaysia is approaching elimination of the human-only Plasmodium species. However, the ongoing increase in P. knowlesi incidence presents a major challenge to malaria control and warrants increased focus on knowlesi-specific prevention activities. Wider molecular surveillance in surrounding countries is required.


2021 ◽  
Author(s):  
Sintayehu Tsegaye Tseha

Malaria is a leading public health problem in tropical and subtropical countries of the world. In 2019, there were an estimated 229 million malaria cases and 409, 000 deaths due malaria in the world. The objective of this chapter is to discuss about the different Plasmodium parasites that cause human malaria. In addition, the chapter discusses about antimalarial drugs resistance. Human malaria is caused by five Plasmodium species, namely P. falciparum, P. malariae, P. vivax, P. ovale and P. knowlesi. In addition to these parasites, malaria in humans may also arise from zoonotic malaria parasites, which includes P. inui and P. cynomolgi. The plasmodium life cycle involves vertebrate host and a mosquito vector. The malaria parasites differ in their epidemiology, virulence and drug resistance pattern. P. falciparum is the deadliest malaria parasite that causes human malaria. P. falciparum accounted for nearly all malarial deaths in 2018. One of the major challenges to control malaria is the emergence and spread of antimalarial drug-resistant Plasmodium parasites. The P. vivax and P. falciparum have already developed resistance against convectional antimalarial drugs such as chloroquine, sulfadoxine-pyrimethamine, and atovaquone. Chloroquine-resistance is connected with mutations in pfcr. Resistance to Sulfadoxine and pyrimethamine is associated with multiple mutations in pfdhps and pfdhfr genes. In response to the evolution of drug resistance Plasmodium parasites, artemisinin-based combination therapies (ACTs) have been used for the treatment of uncomplicated falciparum malaria since the beginning of 21th century. However, artemisinin resistant P. falciparum strains have been recently observed in different parts of the world, which indicates the possibility of the spread of artemisinin resistance to all over the world. Therefore, novel antimalarial drugs have to be searched so as to replace the ACTs if Plasmodium parasites develop resistance to ACTs in the future.


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