Failure to detect Plasmodium vivax in West and Central Africa by PCR species typing

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium vivax </it>is estimated to affect 75 million people annually. It is reportedly absent, however, from west and central Africa due to the high prevalence of the Duffy negative phenotype in the indigenous populations. Despite this, non-African travellers consistently return to their own countries with <it>P. vivax </it>malaria after visiting this region. An attempt was made, therefore, to detect the presence of <it>P. vivax </it>parasites in blood samples collected from the indigenous populations of west and central Africa.</p> <p>Methods</p> <p>Parasite species typing (for all four human malaria parasites) was carried out by PCR on 2,588 blood samples collected from individuals from nine African malaria-endemic countries.</p> <p>Results</p> <p>Most infections (98.5%) were <it>Plasmodium falciparum</it>, <it>Plasmodium malariae </it>was identified in 8.5% of all infections, and <it>Plasmodium ovale </it>in 3.9%. The prevalence of both parasites varied greatly by country. Only one case of <it>P. vivax </it>was detected from Sao Tome, an island off the west coast of Africa, confirming the scarcity of this parasite in Africa.</p> <p>Conclusion</p> <p>The prevalence of <it>P. vivax </it>in local populations in sub-Saharan Africa is very low, despite the frequent identification of this parasite in non-African travellers.</p

A Novel Multi-Observation System to Study the Effects of Anterior Ocular Inflammation in Zinn’s Zonule Using One Specimen

Zinn’s zonule is a fragile and thin tissue, and little is known about its pathogenesis. The aim of this study was to develop an experimental setup for a comprehensive analysis of Zinn’s zonule. Rats were divided into two groups: a control group (n = 4) and an alkali injury group (n = 4). Seven days after injury, the eyes were enucleated, the anterior eye was dissected and embedded in gelatin, and macroscopic observations were made. The gelatin specimens were then embedded in paraffin and observed in detail by low-vacuum scanning electron microscopy, immunofluorescence, and quantitative reverse transcription polymerase chain reaction (RT-qPCR). The results show qualitative changes in Zinn’s zonules in both macroscopic and microscopic observations. In addition, macrophage infiltration and increased matrix metalloproteinase 2 (MMP2) expression were observed in the injured group, consistent with the RT-qPCR results. The experimental system in this study allowed us to capture the morphological and molecular biological changes of Zinn’s zonule and to gain insight into its pathogenesis. In conclusion, this study presents a new experimental setup for the comprehensive analysis of the rat Zinn’s zonule. The results suggest that this system can be used in the future to study and analyze a variety of paraffin-embedded tissues and specimens

皮膚転移によって発見された腎細胞癌の1例

79歳男性.患者は右胸部の無痛性腫瘤を主訴とした.腫瘤を外科的に切除したところ病理組織学的診断ではclear cell carcinoma(alveolar type, Gl)であり, 乳腺組織との関連性は認められなかったため, 胸部皮膚組織への転移巣と考えられた.さらに全身検索を行ったところ, 腹部超音波検査およびMRI検査において右腎下極に内部不均一な腫瘤が認められた.超音波エコーガイド下に針生検を行い病理組織診断を行ったところ, 同じくclear cell carcinoma(alveolar type, Gl)で, これが原発巣だと考えられた.積極的治療を望んだが, 患者より同意を得られず, 現在はインターフェロン-α療法を施行している.なお, 本症例は胸部皮膚転移を契機として腎細胞癌が発見された比較的稀な1例であり, 我が国では23例目の症例報告となったA case of renal cell carcinoma, found after skin metastasis is presented. A 79-year-old man visited Osaka JR hospital, complaining of a painless nodular mass on his right chest. The mass was resected and histopathological examination revealed a clear cell carcinoma (alveolar type, G1) with no involvement of the mammary gland. Abdominal ultrasound and magnetic resonance imaging revealed a heterogenous lower pole mass in the right kidney. Ultrasound-guided needle biopsy of the right renal mass was performed for histopathological diagnosis, which was clear cell carcinoma (alveolar type, G1). At that time, multiple metastases appeared in bilateral lung fields. The patient is currently receiving interferon-alpha therapy, without surgical treatment

マウライ国における熱帯熱マラリア感染に対する抗マラリア薬剤効果 : chloroquineよりsufladoxine/pyrimethamineへの変更7年後の経過

マラウイでは,熱帯熱マラリア患者のchloroquine治療失敗例の増加に伴い,1993年からsulfadoxine/pyrimethamine (SP)がchloroquineに代り導入された.この変更から7年後,我々はサリマ地区の無症候性熱帯熱マラリア感染学童においてin vitroおよびin vivo抗マラリア剤効果,またそれぞれpyrimethamineおよびsulfadoxine耐性と関連する原虫dihydrofolate reductase遺伝子(dhfr)およびdihydropteroate reductase遺伝子(dhps)変異について検討した.対象学童は無作為にchloroquine 3日間の標準投与群(n=50)ないしはSP一回投与群(n=40)に分けられ,治療後28日間にわたり経過が追跡された.In vivoにおけるchloroquineおよびSP感受性率はそれぞれ92%および83%であった.分離熱帯熱マラリア原虫株のin vitro薬剤感受性はSP(n=52),pyrimethamine(52),quinine(36),mefloquine(17)およびamodiaquine(14)に対して検討された.分離株の92%がpyrimethamine耐性を示したにも関わらず,85%はSP感受性であった.Quinineおよびmefloquineに対して検討したすべて,およびamodiaquineに対する93%の分離株はin vitro感受性であった.173例の熱帯熱マラリア感染において,3重変異Asn-108/Ile-51/Arg-59 dhfrおよび2重変異Gly-437/Glu-540 dhpsを持つ原虫が高頻度(78%)で認められた.これらの結果は治療薬剤変更に伴う薬剤圧の減少が原虫chloroquine感受性の回復をもたらしたことを示唆した.高度のpyrimethamineに対するin vitro耐性は高頻度にdhfr3重変異が見られたことと一致した.それにもかかわらず観察された高いSPの効果は,高度pyrimethamine耐性原虫におけるsulfadoxineおよびpyrimethamine間の相乗作用の重要性を示唆した.In Malawi chloroquine was replaced by sulfadoxine/pyrimethamine (SP) in 1993 because of increasing chloroquine treatment failures in Plasmodium falciparum (P.falciparum) patients. Seven years after this change, we studied in vitro and in vivo efficacies of different antimalarial drugs and mutations of dihydrofolate reductase (dhfr)/dihydropteroate synthase (dhps) genes in P. falciparum infections of asymptomatic school children in Salima. The included children were randomly allocated to either treatment group with a standard dose of 3-days chloroquine (n = 50) or a single dose of SP (40) and followed up for 28 days. The in vivo sensitivity rate of chloroquine and SP were 92% and 83% respectively. P.falciparum isolates were successfully evaluated for in vitro drug sensitivity to SP (n = 52), pyrimethamine (52), amodiaquine (14), quinine (36), and mefloquine (17). Although 92% of the isolates were resistant to pyrimethamine, 85% showed in vitro sensitivity to SP. All isolates assessed for quinine and mefloquine and 93% of the isolates for amodiaquine showed in vitro sensitivity. A high prevalence rate (78%) of parasites with triple Asn-108/Ile-51/Arg-59 dhfr and double Gly-437/ Glu-540 dhps mutations was found in 173 P. falciparum infections. Our results suggest that the reduced drug pressure accompanying the policy change consequently resulted in recovery of chloroquine sensitivity in parasites. The high in vitro pyrimethamine resistance was consistent with the high prevalence of the dhfr triple mutant. However, the high efficacy of SP confirmed the important role of synergism between pyrimethamine and sulfadoxine in the treatment of highly pyrimethamine-resistant parasites

マウライ国における熱帯熱マラリア感染に対する抗マラリア薬剤効果 : chloroquineよりsufladoxine/pyrimethamineへの変更7年後の経過

マラウイでは,熱帯熱マラリア患者のchloroquine治療失敗例の増加に伴い,1993年からsulfadoxine/pyrimethamine (SP)がchloroquineに代り導入された.この変更から7年後,我々はサリマ地区の無症候性熱帯熱マラリア感染学童においてin vitroおよびin vivo抗マラリア剤効果,またそれぞれpyrimethamineおよびsulfadoxine耐性と関連する原虫dihydrofolate reductase遺伝子(dhfr)およびdihydropteroate reductase遺伝子(dhps)変異について検討した.対象学童は無作為にchloroquine 3日間の標準投与群(n=50)ないしはSP一回投与群(n=40)に分けられ,治療後28日間にわたり経過が追跡された.In vivoにおけるchloroquineおよびSP感受性率はそれぞれ92%および83%であった.分離熱帯熱マラリア原虫株のin vitro薬剤感受性はSP(n=52),pyrimethamine(52),quinine(36),mefloquine(17)およびamodiaquine(14)に対して検討された.分離株の92%がpyrimethamine耐性を示したにも関わらず,85%はSP感受性であった.Quinineおよびmefloquineに対して検討したすべて,およびamodiaquineに対する93%の分離株はin vitro感受性であった.173例の熱帯熱マラリア感染において,3重変異Asn-108/Ile-51/Arg-59 dhfrおよび2重変異Gly-437/Glu-540 dhpsを持つ原虫が高頻度(78%)で認められた.これらの結果は治療薬剤変更に伴う薬剤圧の減少が原虫chloroquine感受性の回復をもたらしたことを示唆した.高度のpyrimethamineに対するin vitro耐性は高頻度にdhfr3重変異が見られたことと一致した.それにもかかわらず観察された高いSPの効果は,高度pyrimethamine耐性原虫におけるsulfadoxineおよびpyrimethamine間の相乗作用の重要性を示唆した.In Malawi chloroquine was replaced by sulfadoxine/pyrimethamine (SP) in 1993 because of increasing chloroquine treatment failures in Plasmodium falciparum (P.falciparum) patients. Seven years after this change, we studied in vitro and in vivo efficacies of different antimalarial drugs and mutations of dihydrofolate reductase (dhfr)/dihydropteroate synthase (dhps) genes in P. falciparum infections of asymptomatic school children in Salima. The included children were randomly allocated to either treatment group with a standard dose of 3-days chloroquine (n = 50) or a single dose of SP (40) and followed up for 28 days. The in vivo sensitivity rate of chloroquine and SP were 92% and 83% respectively. P.falciparum isolates were successfully evaluated for in vitro drug sensitivity to SP (n = 52), pyrimethamine (52), amodiaquine (14), quinine (36), and mefloquine (17). Although 92% of the isolates were resistant to pyrimethamine, 85% showed in vitro sensitivity to SP. All isolates assessed for quinine and mefloquine and 93% of the isolates for amodiaquine showed in vitro sensitivity. A high prevalence rate (78%) of parasites with triple Asn-108/Ile-51/Arg-59 dhfr and double Gly-437/ Glu-540 dhps mutations was found in 173 P. falciparum infections. Our results suggest that the reduced drug pressure accompanying the policy change consequently resulted in recovery of chloroquine sensitivity in parasites. The high in vitro pyrimethamine resistance was consistent with the high prevalence of the dhfr triple mutant. However, the high efficacy of SP confirmed the important role of synergism between pyrimethamine and sulfadoxine in the treatment of highly pyrimethamine-resistant parasites