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  1. Recent advances on T-cell exhaustion in malaria infection
    Shankar EM, Vignesh R, Dash AP
    Med Microbiol Immunol, 2018 Aug;207(3-4):167-174.
    PMID: 29936565 DOI: 10.1007/s00430-018-0547-0
    T-cell exhaustion reportedly leads to dysfunctional immune responses of antigen-specific T cells. Investigations have revealed that T cells expand into functionally defective phenotypes with poor recall/memory abilities to parasitic antigens. The exploitation of co-inhibitory pathways represent a highly viable area of translational research that has very well been utilized against certain cancerous conditions. Malaria, at times, evolve into a sustained chronic state where T cells express several co-inhibitory molecules (negative immune checkpoints) facilitating parasite escape and sub-optimal protective responses. Experimental evidence suggests that blockade of co-inhibitory molecules on T cells in malaria could result in the sustenance of protective responses together with dramatic parasite clearance. The role of several co-inhibitory molecules in malaria infection largely remain unclear, and here we discussed the potential applicability of co-inhibitory molecules in the management of malaria with a view to harness protective host responses against chronic disease and associated consequences.
    Matched MeSH terms: Malaria/pathology*
  2. Exoerythrocytic schizonts of Plasmodium silvaticum of the orang-utan
    Killick-Kendrick R, Garnham PC, Cheong WH, Cadigan FC, Peters W, Rajapaksa N
    Southeast Asian J. Trop. Med. Public Health, 1972 Sep;3(3):454.
    PMID: 4652473
    Matched MeSH terms: Malaria/pathology
  3. Fulltext Interleukin-27 exhibited anti-inflammatory activity during Plasmodium berghei infection in mice
    Fazalul Rahiman SS, Basir R, Talib H, Tie TH, Chuah YK, Jabbarzare M, et al.
    Trop Biomed, 2013 Dec;30(4):663-80.
    PMID: 24522137 MyJurnal
    Interleukin-27 (IL-27) has a pleiotropic role either as a pro-inflammatory or anti-inflammatory cytokine in inflammatory related diseases. The role and involvement of IL-27 during malaria was investigated and the effects of modulating its release on the production of major inflammatory cytokines and the histopathological consequences in major affected organs during the infection were evaluated. Results showed that IL-27 concentration was significantly elevated throughout the infection but no positive correlation with the parasitaemia development observed. Augmentation of IL-27 significantly elevated the release of anti-inflammatory cytokine, IL-10 whereas antagonising and neutralising IL-27 produced the opposite. A significant elevation of pro-inflammatory cytokines (IFN-γ and IL-6) was also observed, both during augmentation and inhibition of IL-27. Thus, it is suggested that IL-27 exerts an anti-inflammatory activity in the Th1 type response by signalling the production of IL-10 during malaria. Histopathological examination showed sequestration of PRBC in the microvasculature of major organs in malarial mice. Other significant histopathological changes include hyperplasia and hypertrophy of the Kupffer cells in the liver, hyaline membrane formation in lung tissue, enlargement of the white and red pulp followed by the disappearance of germinal centre of the spleen, and tubular vacuolation of the kidney tissues. In conclusion, it is suggested that IL-27 may possibly acts as an anti-inflammatory cytokine during the infection. Modulation of its release produced a positive impact on inflammatory cytokine production during the infection, suggesting its potential in malaria immunotherapy, in which the host may benefit from its inhibition.
    Matched MeSH terms: Malaria/pathology*
  4. Fulltext First case of Plasmodium knowlesi infection in a Japanese traveller returning from Malaysia
    Tanizaki R, Ujiie M, Kato Y, Iwagami M, Hashimoto A, Kutsuna S, et al.
    Malar J, 2013;12:128.
    PMID: 23587117 DOI: 10.1186/1475-2875-12-128
    This is the first case of Plasmodium knowlesi infection in a Japanese traveller returning from Malaysia. In September 2012, a previously healthy 35-year-old Japanese man presented to National Center for Global Health and Medicine in Tokyo with a two-day history of daily fever, mild headaches and mild arthralgia. Malaria parasites were found in the Giemsa-stained thin blood smear, which showed band forms similar to Plasmodium malariae. Although a nested PCR showed the amplification of the primer of Plasmodium vivax and Plasmodium knowlesi, he was finally diagnosed with P. knowlesi mono-infection by DNA sequencing. He was treated with mefloquine, and recovered without any complications. DNA sequencing of the PCR products is indispensable to confirm P. knowlesi infection, however there is limited access to DNA sequencing procedures in endemic areas. The extent of P. knowlesi transmission in Asia has not been clearly defined. There is limited availability of diagnostic tests and routine surveillance system for reporting an accurate diagnosis in the Asian endemic regions. Thus, reporting accurately diagnosed cases of P. knowlesi infection in travellers would be important for assessing the true nature of this emerging human infection.
    Matched MeSH terms: Malaria/pathology*
  5. Fulltext Review of cases with the emerging fifth human malaria parasite, Plasmodium knowlesi
    Kantele A, Jokiranta TS
    Clin Infect Dis, 2011 Jun;52(11):1356-62.
    PMID: 21596677 DOI: 10.1093/cid/cir180
    Human malaria has been known to be caused by 4 Plasmodium species, with Plasmodium falciparum causing the most-severe disease. Recently, numerous reports have described human malaria caused by a fifth Plasmodium species, Plasmodium knowlesi, which usually infects macaque monkeys. Hundreds of human cases have been reported from Malaysia, several cases have been reported in other Southeast Asian countries, and a few cases have been reported in travelers visiting these areas. Similarly to P. falciparum, P. knowlesi can cause severe and even fatal cases of disease that are more severe than those caused by the other Plasmodium species. Polymerase chain reaction is of value for diagnosis because P. knowlesi infection is easily misdiagnosed as less dangerous Plasmodium malariae infection with conventional microscopy. P. knowlesi infection should be suspected in patients who are infected with malaria in Southeast Asia. If human-mosquito-human transmission were to occur, the disease could spread to new areas where the mosquito vectors live, such as the popular tourist areas in western India.
    Matched MeSH terms: Malaria/pathology
  6. Fulltext Plasmodium knowlesi genome sequences from clinical isolates reveal extensive genomic dimorphism
    Pinheiro MM, Ahmed MA, Millar SB, Sanderson T, Otto TD, Lu WC, et al.
    PLoS One, 2015;10(4):e0121303.
    PMID: 25830531 DOI: 10.1371/journal.pone.0121303
    Plasmodium knowlesi is a newly described zoonosis that causes malaria in the human population that can be severe and fatal. The study of P. knowlesi parasites from human clinical isolates is relatively new and, in order to obtain maximum information from patient sample collections, we explored the possibility of generating P. knowlesi genome sequences from archived clinical isolates. Our patient sample collection consisted of frozen whole blood samples that contained excessive human DNA contamination and, in that form, were not suitable for parasite genome sequencing. We developed a method to reduce the amount of human DNA in the thawed blood samples in preparation for high throughput parasite genome sequencing using Illumina HiSeq and MiSeq sequencing platforms. Seven of fifteen samples processed had sufficiently pure P. knowlesi DNA for whole genome sequencing. The reads were mapped to the P. knowlesi H strain reference genome and an average mapping of 90% was obtained. Genes with low coverage were removed leaving 4623 genes for subsequent analyses. Previously we identified a DNA sequence dimorphism on a small fragment of the P. knowlesi normocyte binding protein xa gene on chromosome 14. We used the genome data to assemble full-length Pknbpxa sequences and discovered that the dimorphism extended along the gene. An in-house algorithm was developed to detect SNP sites co-associating with the dimorphism. More than half of the P. knowlesi genome was dimorphic, involving genes on all chromosomes and suggesting that two distinct types of P. knowlesi infect the human population in Sarawak, Malaysian Borneo. We use P. knowlesi clinical samples to demonstrate that Plasmodium DNA from archived patient samples can produce high quality genome data. We show that analyses, of even small numbers of difficult clinical malaria isolates, can generate comprehensive genomic information that will improve our understanding of malaria parasite diversity and pathobiology.
    Matched MeSH terms: Malaria/pathology
  7. Plasmodium hylobati: a malaria parasite of the gibbon
    Collins WE, Contacos PG, Garnham PC, Warren M, Skinner JC
    J Parasitol, 1972 Feb;58(1):123-8.
    PMID: 4335047
    Matched MeSH terms: Malaria/pathology
  8. Studies on Plasmodium gallinaceum and Plasmodium juxtanucleare from the Malayan jungle fowl Gallue gallus spadiceus
    Fernando MA, Dissanaike AS
    Southeast Asian J. Trop. Med. Public Health, 1975 Mar;6(1):25-32.
    PMID: 806969
    Matched MeSH terms: Malaria/pathology
  9. Fulltext The dangers of accepting a single diagnosis: case report of concurrent Plasmodium knowlesi malaria and dengue infection
    Chong SE, Mohamad Zaini RH, Suraiya S, Lee KT, Lim JA
    Malar J, 2017 01 03;16(1):2.
    PMID: 28049485 DOI: 10.1186/s12936-016-1666-y
    BACKGROUND: Dengue and malaria are two common, mosquito-borne infections, which may lead to mortality if not managed properly. Concurrent infections of dengue and malaria are rare due to the different habitats of its vectors and activities of different carrier mosquitoes. The first case reported was in 2005. Since then, several concurrent infections have been reported between the dengue virus (DENV) and the malaria protozoans, Plasmodium falciparum and Plasmodium vivax. Symptoms of each infection may be masked by a simultaneous second infection, resulting in late treatment and severe complications. Plasmodium knowlesi is also a common cause of malaria in Malaysia with one of the highest rates of mortality. This report is one of the earliest in literature of concomitant infection between DENV and P. knowlesi in which a delay in diagnosis had placed a patient in a life-threatening situation.

    CASE PRESENTATION: A 59-year old man staying near the Belum-Temengor rainforest at the Malaysia-Thailand border was admitted with fever for 6 days, with respiratory distress. His non-structural protein 1 antigen and Anti-DENV Immunoglobulin M tests were positive. He was treated for severe dengue with compensated shock. Treating the dengue had so distracted the clinicians that a blood film for the malaria parasite was not done. Despite aggressive supportive treatment in the intensive care unit (ICU), the patient had unresolved acidosis as well as multi-organ failure involving respiratory, renal, liver, and haematological systems. It was due to the presentation of shivering in the ICU, that a blood film was done on the second day that revealed the presence of P. knowlesi with a parasite count of 520,000/μL. The patient was subsequently treated with artesunate-doxycycline and made a good recovery after nine days in ICU.

    CONCLUSIONS: This case contributes to the body of literature on co-infection between DENV and P. knowlesi and highlights the clinical consequences, which can be severe. Awareness should be raised among health-care workers on the possibility of dengue-malaria co-infection in this region. Further research is required to determine the real incidence and risk of co-infection in order to improve the management of acute febrile illness.

    Matched MeSH terms: Malaria/pathology
  10. Fulltext The application of biomedical engineering techniques to the diagnosis and management of tropical diseases: a review
    Ibrahim F, Thio TH, Faisal T, Neuman M
    Sensors (Basel), 2015 Mar 23;15(3):6947-95.
    PMID: 25806872 DOI: 10.3390/s150306947
    This paper reviews a number of biomedical engineering approaches to help aid in the detection and treatment of tropical diseases such as dengue, malaria, cholera, schistosomiasis, lymphatic filariasis, ebola, leprosy, leishmaniasis, and American trypanosomiasis (Chagas). Many different forms of non-invasive approaches such as ultrasound, echocardiography and electrocardiography, bioelectrical impedance, optical detection, simplified and rapid serological tests such as lab-on-chip and micro-/nano-fluidic platforms and medical support systems such as artificial intelligence clinical support systems are discussed. The paper also reviewed the novel clinical diagnosis and management systems using artificial intelligence and bioelectrical impedance techniques for dengue clinical applications.
    Matched MeSH terms: Malaria/pathology
  11. Fulltext Human infections and detection of Plasmodium knowlesi
    Singh B, Daneshvar C
    Clin Microbiol Rev, 2013 Apr;26(2):165-84.
    PMID: 23554413 DOI: 10.1128/CMR.00079-12
    Plasmodium knowlesi is a malaria parasite that is found in nature in long-tailed and pig-tailed macaques. Naturally acquired human infections were thought to be extremely rare until a large focus of human infections was reported in 2004 in Sarawak, Malaysian Borneo. Human infections have since been described throughout Southeast Asia, and P. knowlesi is now recognized as the fifth species of Plasmodium causing malaria in humans. The molecular, entomological, and epidemiological data indicate that human infections with P. knowlesi are not newly emergent and that knowlesi malaria is primarily a zoonosis. Human infections were undiagnosed until molecular detection methods that could distinguish P. knowlesi from the morphologically similar human malaria parasite P. malariae became available. P. knowlesi infections cause a spectrum of disease and are potentially fatal, but if detected early enough, infections in humans are readily treatable. In this review on knowlesi malaria, we describe the early studies on P. knowlesi and focus on the epidemiology, diagnosis, clinical aspects, and treatment of knowlesi malaria. We also discuss the gaps in our knowledge and the challenges that lie ahead in studying the epidemiology and pathogenesis of knowlesi malaria and in the prevention and control of this zoonotic infection.
    Matched MeSH terms: Malaria/pathology
  12. In vivo study of human Plasmodium knowlesi in Macaca fascicularis
    Anderios F, Noorrain A, Vythilingam I
    Exp Parasitol, 2010 Feb;124(2):181-9.
    PMID: 19765587 DOI: 10.1016/j.exppara.2009.09.009
    Plasmodium knowlesi is a malaria parasite of Old World monkeys and is infectious to humans. In this study Macaca fascicularis was used as a model to understand the host response to P. knowlesi using parasitological and haematological parameters. Three M. fascicularis of either sex were experimentally infected with P. knowlesi erythrocytic parasites from humans. The pre-patent period for P. knowlesi infection in M. fascicularis ranged from seven to 14 days. The parasitemia observed was 13,686-24,202 parasites per microL of blood for asexual stage and 88-264 parasites per microL of blood for sexual stage. Periodicity analysis adopted from microfilaria periodicity technique of asexual stage showed that the parasitemia peak at 17:39h while the sexual stage peaked at 02:36 h. Mathematical analysis of the data indicates that P. knowlesi gametocytes tend to display periodicity with a peak (24:00-06:00) that coincides with the peak biting activity (19:00-06:00) of the local vector, Anopheles latens. The morphology of P. knowlesi resembled P. falciparum in early trophozoite and P. malariae in late trophozoite. However, it may be distinguishable by observing the appliqué appearance of the cytoplasm and the chromatin lying inside the ring. Haematological analysis on macaques with knowlesi malaria showed clinical manifestations of hypoglycaemia, anaemia and hyperbilirubinemia. Gross examination of spleen and liver showed malaria pigments deposition in both organs.
    Matched MeSH terms: Malaria/pathology
  13. Pathologic activity of Plasmodium berghei prevented but not reversed by dexamethasone
    Franz DR, Lim TS, Baze WB, Arimbalam S, Lee M, Lewis GE
    Am J Trop Med Hyg, 1988 Mar;38(2):249-54.
    PMID: 3281490
    Dexamethasone has recently been shown to block the production of cachectin (implicated in the pathogenesis of cerebral malaria) if administered prior to endotoxin induction of mouse macrophages. Using the hamster cheek pouch-cerebral malaria model, we tested the hypothesis that dexamethasone is effective as a therapeutic agent in severe malaria if given before some yet undefined trigger point in the disease. Infected hamsters were treated with dexamethasone (0.7 mg/kg) daily on days 7-12, 4-12, or 1-12 post-challenge. When treatment was started on day 1, whole body oxygen consumption (used as a measure of erythrocyte transport to sites of diffusion) on day 12 was greater than (P less than 0.05) that of infected control animals, though the degree of anemia was no different in treated and untreated groups. Furthermore, treatment produced a reduction in monocyte accumulation, capillary malfunction, and monocyte/red blood cell aggregate formation observable in the cheek pouch in vivo and a similar reduction in monocyte presence, capillary pathologic change, and multifocal hemorrhage in the brain on postmortem. These data suggest that mediator(s), whose production can be blocked by pretreatment with dexamethasone, are involved in the pathogenesis of disease leading to death of the Plasmodium berghei infected hamster.
    Matched MeSH terms: Malaria/pathology
  14. Fulltext Clinical situation of endemic malaria in Yemen
    Abdulsalam M Q AM, Mohammed A K M, Ahmed A A, Fong MY
    Trop Biomed, 2010 Dec;27(3):551-8.
    PMID: 21399597 MyJurnal
    Malaria remains a major public health problem causing mortality and morbidity in tropical and subtropical countries. A cross-sectional study was carried out to determine malaria prevalence and its clinical pattern during malaria season in Yemen. Blood samples were collected from 511 patients with fever who voluntary participated in this study, of them 268 were males and 242 females. Malaria was screened using Giemsa-stained thick and thin blood films. Clinical profile was recorded through physical and laboratory examinations and biodata were collected by pre-tested standard questionnaire. The overall prevalence was 15.3%. Three malaria species (Plasmodium falciparum, Plasmodium vivax and Plasmodium malarae) were detected with the predominance of P. falciparum (83.33%). People living in the rural areas had higher infection rate compared to urban areas (p < 0.005). Children were at higher risk of developing severe malaria compared to adults (p < 0.05). Severe anaemia, respiratory distress, jaundice, convulsion and bleeding were more apparent among younger age groups of malaria cases compared to older children. The study indicates that malaria is still a public health problem with children being at high risk of developing severe malaria which may lead to death.
    Matched MeSH terms: Malaria/pathology*
  15. Fulltext Platelets kill circulating parasites of all major Plasmodium species in human malaria
    Kho S, Barber BE, Johar E, Andries B, Poespoprodjo JR, Kenangalem E, et al.
    Blood, 2018 Sep 20;132(12):1332-1344.
    PMID: 30026183 DOI: 10.1182/blood-2018-05-849307
    Platelets are understood to assist host innate immune responses against infection, although direct evidence of this function in any human disease, including malaria, is unknown. Here we characterized platelet-erythrocyte interactions by microscopy and flow cytometry in patients with malaria naturally infected with Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium knowlesi Blood samples from 376 participants were collected from malaria-endemic areas of Papua, Indonesia, and Sabah, Malaysia. Platelets were observed binding directly with and killing intraerythrocytic parasites of each of the Plasmodium species studied, particularly mature stages, and was greatest in P vivax patients. Platelets preferentially bound to the infected more than to the uninfected erythrocytes in the bloodstream. Analysis of intraerythrocytic parasites indicated the frequent occurrence of platelet-associated parasite killing, characterized by the intraerythrocytic accumulation of platelet factor-4 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling of parasite nuclei (PF4+TUNEL+ parasites). These PF4+TUNEL+ parasites were not associated with measures of systemic platelet activation. Importantly, patient platelet counts, infected erythrocyte-platelet complexes, and platelet-associated parasite killing correlated inversely with patient parasite loads. These relationships, taken together with the frequency of platelet-associated parasite killing observed among the different patients and Plasmodium species, suggest that platelets may control the growth of between 5% and 60% of circulating parasites. Platelet-erythrocyte complexes made up a major proportion of the total platelet pool in patients with malaria and may therefore contribute considerably to malarial thrombocytopenia. Parasite killing was demonstrated to be platelet factor-4-mediated in P knowlesi culture. Collectively, our results indicate that platelets directly contribute to innate control of Plasmodium infection in human malaria.
    Matched MeSH terms: Malaria/pathology
  16. Fulltext Anti-malarial and anti-inflammatory effects of Gleichenia truncata mediated through inhibition of GSK3β
    Suhaini S, Liew SZ, Norhaniza J, Lee PC, Jualang G, Embi N, et al.
    Trop Biomed, 2015 Sep;32(3):419-33.
    PMID: 26695202 MyJurnal
    Gleichenia truncata is a highland fern from the Gleicheniaceae family known for its traditional use among indigenous communities in Asia to treat fever. The scientific basis of its effect has yet to be documented. A yeast-based kinase assay conducted in our laboratory revealed that crude methanolic extract (CME) of G. truncata exhibited glycogen synthase kinase-3 (GSK3)-inhibitory activity. GSK3β is now recognized to have a pivotal role in the regulation of inflammatory response during bacterial infections. We have also previously shown that lithium chloride (LiCl), a GSK3 inhibitor suppressed development of Plasmodium berghei in a murine model of malarial infection. The present study is aimed at evaluating G. truncata for its anti-malarial and anti-inflammatory effects using in vivo malarial and melioidosis infection models respectively. In a four-day suppressive test, intraperitoneal injections of up to 250 mg/kg body weight (bw) G. truncata CME into P.berghei-infected mice suppressed parasitaemia development by >60%. Intraperitoneal administration of 150 mg/kg bw G. truncata CME into Burkholderia pseudomallei-infected mice improved survivability by 44%. G. truncata CME lowered levels of pro-inflammatory cytokines (TNF-α, IFN-γ) in serum and organs of B. pseudomallei-infected mice. In both infections, increased phosphorylations (Ser9) of GSK3β were detected in organ samples of animals administered with G. truncata CME compared to controls. Taken together, results from this study strongly suggest that the anti-malarial and anti-inflammatory effects elicited by G. truncata in part were mediated through inhibition of GSK3β. The findings provide scientific basis for the ethnomedicinal use of this fern to treat inflammation-associated symptoms.
    Matched MeSH terms: Malaria/pathology
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