Aminoquinolines susceptibility of Plasmodium falciparum clones from Nouna Burkina Faso Africa

We observed a declining trend in malaria transmission at Nouna, Burkina Faso during the rainy season from 2009-2011. Single and mixed infections for Plasmodium falciparum and Plasmodium malariae were significantly reduced compared to the baseline data (rainy season 2000) and a lower prevalence of P. malariae was associated with a reduced transmission intensity. Microscopic examination has a lower detection limit and is associated with under-estimation of parasite burden, which suggested the use of molecular diagnosis such as PCR as a more sensitive method in determining the prevalence of malaria infections. Amodiaquine (AQ) is an antimalarial compound chemically and functionally related to chloroquine (CQ). Currently, it is used in combination with artesunate (AS) as the first choice to treat uncomplicated P. falciparum malaria in some countries in Africa and South America. Chloroquine-resistant parasites and cross-resistance between CQ and AQ or its active metabolite Desethyl-amodiaquine (DQ) have been observed in Burkina Faso. pfcrt and pfmdr1 are genes genetically associated with the resistance mechanism and the underlying mechanisms for cross-resistance are still under debate. The main aim of this study was to assess the susceptibility patterns of clonal field isolates P. falciparum compared to reference laboratory strains (Dd2 and HB3). Blood samples from 402 patients from the village Bourasso, Nouna, Burkina Faso were analysed. Genomic DNA was extracted from filter papers using the Chelex-100 method and different Plasmodium species were analysed by microscopy and species-specific nested-PCR. The mutation in pfcrt which was associated with CQ and AQ resistance was analysed using pyrosequencing, and in vitro susceptibility of clonal parasites to CQ, AQ and DQ was determined. Three different phenotypes of P. falciparum (S9, S47, S173) based on the IC50 values were cultured and the clonal lines were obtained. All clones from S9 and S47 harboured pfcrt CVIET haplotypes while all clones from S173 were CVMNK haplotype. The clones from S9 showed higher IC50 values on average to CQ and AQ compared to S47 clonal parasites. Some clones were sensitive to DQ for S9 and all were sensitive in clonal lines for sample 47. Clonal parasites from S173 has lower IC50 values towards CQ. Responses to CQ, AQ and DQ varied between the clones. Clear cross-resistance were observed in clonal lines S9, eg. 9C9, 9C7, 9H8 and in clone S47E8. There was a moderate correlation between AQ and DQ and a weaker correlation between AQ and CQ. Cross resistance exists but not high in the clonal lines. After a consistence result of IC50, 9C6, 47C7 and 173D3 were selected for the drug accumulation study. Accumulation of CQ and AQ does not always correlate with IC50. It appeared that clones accumulating high levels of CQ and AQ were susceptible to CQ and AQ respectively, while clones accumulating lower CQ and AQ were resistant. High CQ and AQ IC50 values were associated with lower amounts of drug uptake and the two response parameters reciprocally correlated to each other. Long-term and continuous culture can cause loss of the resistance phenotype. From the observations and findings of this study, we concluded that Pfcrt plays a major role in the resistance to CQ and AQ and we suggest that one or more genes or SNPs may be involved in AQ drug resistance. There were no resistant clones isolated from the in-vitro selection strategy after challenge with 60 nM DQ but suggested dormant parasites to DQ developed after the exposure. After investigation using quantitative recrudescence assays, the parasites were not dormant but were in fact dead. Several strategies and processes could be improved for future studies to select for AQ resistant parasites

Taburan parasit anura dan indeks kualiti air di kawasan tasik dan Tanah Bencah Putrajaya

Populasi anura (katak) di sesuatu ekosistem boleh menjadi penunjuk biologi bagi tahap kebersihan. Populasi yang rendah atau kadar kematian anura yang tinggi di sesuatu persekitaran menunjukkan ekosistem kawasan tersebut adalah tidak stabil, contohnya akibat pencemaran air atau kadar jangkitan parasit yang tinggi. Objektif kajian ini adalah untuk menentukan kepelbagaian spesies anura, mengenal pasti taburan parasit yang menjangkiti anura di kawasan tasik dan Tanah Bencah Putrajaya dan menentukan hubungan antara indeks kualiti air dengan taburan parasit dan anura. Sebanyak 74 ekor katak telah ditangkap sepanjang tempoh persampelan yang tergolong daripada lima famili dan enam spesies yang berbeza. Indeks kepelbagaian Shannon menunjukkan stesen LE, UN, UW, P.7 dan P.10 mempunyai nilai indeks kepelbagaian iaitu 1˗3 bermaksud kepelbagaian spesies anura adalah sederhana. Sebanyak 2437 ekor parasit telah ditemui pada semua 74 ekor katak yang telah dibedah dalam kajian ini. Anggaran 86.5% katak di kawasan Putrajaya telah dijangkiti parasit. Status indeks kualiti air bagi kesemua stesen Putrajaya adalah bersih hingga sederhana bersih (kelas II hingga III). Ujian Kruskal-Wallis mendapati bahawa taburan parasit pada anura di setiap stesen UE, UW, UN, LE, CW, P.7, dan P.10 adalah tidak signifikan (X² =9.28; df=6; p>0.05). Ini bermaksud tiada perbezaan signifikan antara taburan parasit pada anura di setiap kawasan dan jangkitan parasit ini adalah tidak dipengaruhi oleh indeks kualiti air di sesuatu stesen kajian

Gastrointestinal parasites in Macaca fascicularis living in two urban areas of Malaysia

Macaca fascicularisor commonly known as long-tailed macaques,are nonhuman primates that are increasingly vulnerable in becoming natural reservoirs for many microorganisms including gastrointestinal (GI) parasites, largely due to anthropogenic activities. This study was conducted to detect and compare GI parasites in M. fascicularisfound in densely urbanized settings. The fecal samples of the long-tailed macaques were collected at a public university campus (Universiti Kebangsaan Malaysia, Bangi) and a tourist site (Bukit Melawati, Kuala Selangor). A total of 80 fecal samples were collected: 50 at the university campus, and the remaining samples from the tourist site. The fecal samples were processed by flotation techniques to include the GI parasites and then were subjected tomorphological analysis to identify important taxonomy keys under microscopic magnification. A total of 139 parasites were identified from both locations and classified into 5 phylums and 17 families. Among the 139 parasites, 33 parasites were grouped into 6 genus of GI parasites. Among the gastrointestinal parasites that were identified from both study sites, three parasites were zoonotic namely Strongyloidsspp., Trichostrongylusspp.and Trichurisspp.Results showed that the diversity index of GI parasites was higher at the university campus compared to the tourist site with Simpson’s Index values of 0.953 and 0.880, respectively, while the Shannon’s Index values were 3.282 and 2.399, respectively. This research revealed that there are more parasite infections in the long-tailed macaques in the campus surroundings compared to those found in the tourist site. Therefore, it is highly suggested that authority intervention by translocating the long-tailed macaques elsewhere is necessary to avoid prolonged contact and possible parasite transmission to humans, and if any parasitic infections occur, appropriate medication such as anthelmintic drugs should be readily available at the university campus clinics

Pengesanan dan pencirian Leptospira spp. pada haiwan liar dan persekitaran di pusat pemuliharaan ex situ

Leptospirosis ialah penyakit berjangkit yang disebabkan oleh bakteria Leptospira yang boleh menjangkiti manusia dan haiwan. Kajian ini dijalankan bagi mengenal pasti jangkitan leptospirosis yang berkitar antara orang utan, roden dan persekitaran di Pulau Orang Utan Bukit Merah (BMOUI) dan Zoo Taiping, Perak. Sampel haiwan serta persekitaran yang diperoleh dari kedua-dua kawasan kajian diinokulasi dalam media Ellinghausen-Mccullough�Johnson-Harris (EMJH) untuk pengkulturan Leptospira. Pengesanan dan pencirian mudah spesies Leptospira melalui PCR dilakukan ke atas kultur serta sampel haiwan yang positif. Pencirian spesies yang lebih mendalam sehingga peringkat serovar menggunakan penjenisan jujukan multi-lokus (MLST) hanya dilakukan ke atas kultur patogenik sahaja. Sebanyak 8/14 kultur daripada sampel persekitaran BMOUI merupakan spesies saprofitik (L. yanagawae, L. meyeri dan L. idonii), 4/14 adalah spesies perantaraan (L. wolffii) dan 2/14 (dilabel sebagai ‘Soil2’ dan ‘BJ3 soil’) adalah spesies patogenik. Hasil MLST menunjukkan kultur ‘Soil2’ telah dikenal pasti sebagai L. interrogans serovar Lai Langkawi dengan nilai penjenisan jujukan, ST: 236. ‘BJ3 soil’ pula telah diberikan profil alel baharu yang menjana nilai ST baharu iaitu 262 di bawah spesies L. kmetyi. Kesemua 15/15 kultur daripada sampel persekitaran Zoo Taiping merupakan spesies saprofit (L. yanagawae dan L. meyeri). Leptospira yang dikesan secara langsung dalam sampel orang utan dan tikus dari BMOUI berkait rapat dengan spesies L. wolffii. Sampel orang utan dari Zoo Taiping pula berkait rapat dengan spesies L. kmetyi dan L. wolffii. Kajian ini berjaya membuktikan bahawa berlakunya transmisi leptospirosis di BMOUI dan Zoo Taiping yang sememangnya amat penting dalam menambahbaik strategi pencegahan penyakit ini sekaligus membantu dalam usaha pemuliharaan orang utan

Pencirian jangkitan Plasmodium berghei NK65 pada mencit ICR sebagai model jangkitan malaria teruk

Malaria teruk atau ‘severe’ kebiasaannya disebabkan oleh jangkitan Plasmodium falciparum. Jangkitan Plasmodium falciparum pada manusia boleh menyebabkan kerosakan organ, anemia teruk, komplikasi serius, koma dan kematian. Bagi tujuan memahami patogenesis malaria teruk, model haiwan digunakan dalam kajian kali ini bagi mengenal pasti sama ada gabungan hos-parasit daripada mencit ICR dengan Plasmodium berghei NK65 boleh menyebabkan jangkitan malaria teruk pada hos. Pencirian jangkitan P. berghei ANKA pernah dilakukan sebelum ini terhadap mencit ICR; walau bagaimanapun, pencirian jangkitan P. berghei NK65 secara terperinci terhadap mencit ICR dalam kajian ini adalah pertama kali dilaporkan. Inokulasi sel darah merah (RBC) terjangkit-P. berghei NK65 (2 × 107 parasit RBC (pRBC)/ mL) dilakukan terhadap mencit ICR dengan suntikan secara intraperitoneum. Pemantauan perubahan ciri fizikal seperti berat, suhu mencit, kematian mencit, pos mortem, histologi dan aras sitokin inflamasi yang terhasil selepas jangkitan direkod untuk analisis. Strain P. berghei NK65 menghasilkan jangkitan tahap teruk terhadap mencit ICR iaitu paras parasitemia melebihi 50% pada hari ke-10 selepas jangkitan diikuti kematian. Analisis histopatologi menunjukkan jangkitan ini menyebabkan perubahan pada tisu serebrum, perlekatan leukosit pada endotelium dan pensekuesteran pRBC dalam salur darah serebrum serta pendarahan intravaskular. Selepas jangkitan, pensekuesteran pRBC dan pengumpulan pigmen malaria turut dilihat pada organ utama mencit. Tambahan lagi, edema pulmonari, pembentukan membran hialin pada peparu dan pendarahan kortikal pada ginjal dilihat pada mencit terjangkit. Sitokin proinflamasi (TNF-α, IFN-γ, dan IL-18) dan sitokin antiinflamasi (IL-10 dan IL-4) juga meningkat dalam serum mencit terjangkit. Secara rumusannya, model jangkitan mencit ICR-P. berghei NK65 yang digunakan dalam kajian ini menunjukkan ciri-ciri jangkitan malaria teruk. Hasil daripada kajian ini boleh digunakan sebagai asas untuk memahami patogenesis bagi malaria teruk pada manusia dan model jangkitan malaria haiwan pada masa akan datang

Sintesis, aktiviti antiplasmodium dan kesitotoksikan secara in vitro sebatian porfirin logam ke atas strain Plasmodium falciparum K1

Jangkitan malaria adalah penyakit berjangkit serius yang disebabkan oleh parasit plasmodium dan harus dirawat sebagai perubatan kecemasan. Sehingga kini, tiada vaksin yang sudah dikomersialkan untuk mencegah malaria. Enam sebatian porfirin logam nikel(II) dan zink(II) berasaskan porfirinmeso bebas bes 5,15-difenilporfirin (2), 5,15-diheksilporfirin (3) dan 5,10,15,20-tetrafenilporfirin (4) iaitu NiDDHP, NiDPP, NiTPP, ZnDHP, ZnDPP dan ZnTPP dihasilkan melalui penyejatan Lindsey sebelum dicirikan secara spektroskopi (resonans magnet nukleus, ultra lembayung boleh nampak, spektrometri jisim) dan fizikal (takat lebur). Aktiviti antiplasmodium dan kesitotoksikan secarain vitro terhadap strain rintang-klorokuina, P. falciparum K1 dinilai dan dibandingkan dengan aktiviti antiplasmodium dadah rujukan seperti klorokuina dan artemisinin. ZnDHP, ZnTPP dan NiDPP merencat pertumbuhan parasit dengan 50% kepekatan perencatan berkesan (EC50) dalam julat aktiviti antiplasmodium sederhana iaitu 21.4 sehingga 36.0 µM. Aktiviti kesitotoksikan terhadap sel mamalia Vero yang ditunjukkan oleh NiDPP, ZnDHP dan ZnTPP berada dalam julat tidak toksik iaitu 97 sehingga 587 µM. ZnDHP mempunyai nilai indeks pemilihan yang paling tinggi iaitu 27.2 µM, menunjukkan aktiviti antiplasmodium yang selektif terhadap perencatan plasmodium dan tidak toksik terhadap sel mamalia

Prevalence of simian malaria among macaques in Malaysia (2000–2021): A systematic review

Background The aim of Malaysia to eliminate malaria nationwide by 2020 seems need to be prolonged. Whilst Malaysia has successfully eliminated human malaria transmission, simian malaria parasites such as Plasmodium knowlesi, P. cynomolgi, P. inui and P. cynomolgi are the emerging cause of malaria in humans. The epidemiological study of simian malaria in primates provides useful information in identifying the risk of human-macaques Plasmodium infection. Methodology/Principal findings This study was performed to gather all available data in terms of simian malaria epidemiology study among macaques in Malaysia over the last two decades. This systematic review was conducted according to the PRISMA guidelines to select appropriate articles as references. Data searches were performed through international databases such as Google Scholar, PubMed, CrossRef, Scopus, Web of Science and Science Direct for original articles published from 2000 until 2021. The review identified seven simian malaria epidemiology studies in Malaysia over the 20-year study period. Most studies were conducted in Peninsular Malaysia (5/7; 71%) followed by East Malaysia (2/7; 29%). All studies showed positive detection of Plasmodium parasites in macaques. The most prevalent Plasmodium species in macaques was P. inui (49.27%) and the least prevalent was P. fieldi (4.76%). The prevalence of simian malaria was higher in East Malaysia compared to Peninsular Malaysia. The mono, dual and triple infection types were the most common among macaques. Conclusion/Significance The non-human primates like macaques are the reservoir of simian plasmodium in Malaysia. Hence, the study of host epidemiology is an important insight to public health management as there is a high occurrence of simian malaria in Malaysia. The right measurement can be taken as well to prevent the transmission of simian malaria from macaques to humans. Author summary Macaques are the most abundant primates in south east Asia including Malaysia. Due to deforestation, macaques came closer to human settlements searching for food. Macaques like the long-tailed and pig-tailed harbouring several Plasmodium species that can cause zoonotic malaria in humans. Close contact of human and macaques cause zoonotic transmission of simian malaria. The simian plasmodium such as P. knowlesi, P. inui and P. cynomolgi have been found infecting humans in Malaysia; mainly in East Malaysia (Borneo). Zoonotic malaria poses great risk to public health as prolonged in treatment often lead to fatal outcomes. Hence the knowledge of prevalence and diversity is important to access, this can therefore enlighten the authorities to plan a control strategy that will minimize the zoonotic transmission between non-human primate host to human. This systematic review has summarised all publish data of macaques-plasmodium infection from the year 2000–2021 by using PRISMA guidelines. Our result showed that P. inui (49.27%) is the most prevalent Plasmodium species found in macaques, followed by P. cynomolgi (33.05%) and P. knowlesi (26.86%). Simian plasmodium prevalent was also found higher in East Malaysia (97.0%) compared to Peninsular Malaysia (45.18%). The significant increase of simian malaria incidences in human have jeopardized the national malaria elimination programme. Hence, this study provides a compact insight into the plasmodium epidemiology of macaques in Malaysia

Detection of Leptospira kmetyi at recreational areas in Peninsular Malaysia

Humans can be infected by pathogenic Leptospira through contact with infected animals or contaminated environments. Recreational exposure has been associated with human leptospirosis; however, there is a lack of information on the distribution of Leptospira spp. in recreational areas. Thus, we conducted this study to detect and describe the distributions of Leptospira spp. and to determine the prevalence of pathogenic leptospires at recreational areas in Peninsular Malaysia. Soil and water samples were randomly collected from 33 recreational areas in Peninsular Malaysia from December 2018 to April 2019. Each culture was examined under dark-field microscopy prior to genus confirmation by polymerase chain reaction using primers for the 16S rRNA gene. A total of 390 water and soil samples were collected, and 131 cultures were positive for Leptospira under dark-field microscope examination. Leptospira was identified in most of the recreational areas sampled, and at least one pathogenic Leptospira species was isolated from 17 recreational areas. The prevalence of saprophytic, intermediate, and pathogenic Leptospira spp. was 19.7%, 5.6%, and 8.2%, respectively. The dominant pathogenic species found in the samples was Leptospira kmetyi. This study provides important data on the distribution and prevalence of Leptospira spp. from soil and water, as well as the dominant pathogenic species, at recreational areas in Peninsular Malaysia. Therefore, preventive measures should be taken to ensure the safety of visitors

Curcumin and Its Derivatives as Potential Antimalarial and Anti-Inflammatory Agents: A Review on Structure–Activity Relationship and Mechanism of Action

Curcumin, one of the major ingredients of turmeric (Curcuma longa), has been widely reported for its diverse bioactivities, including against malaria and inflammatory-related diseases. However, curcumin’s low bioavailability limits its potential as an antimalarial and anti-inflammatory agent. Therefore, research on the design and synthesis of novel curcumin derivatives is being actively pursued to improve the pharmacokinetic profile and efficacy of curcumin. This review discusses the antimalarial and anti-inflammatory activities and the structure–activity relationship (SAR), as well as the mechanisms of action of curcumin and its derivatives in malarial treatment. This review provides information on the identification of the methoxy phenyl group responsible for the antimalarial activity and the potential sites and functional groups of curcumin for structural modification to improve its antimalarial and anti-inflammatory actions, as well as potential molecular targets of curcumin derivatives in the context of malaria and inflammation