Kariuki Christopher, Kagira John M, Mwadime Victor, Ngotho Maina
Institute of Primate Research, Kenya.
Jomo Kenyatta University of Agriculture and Technology, Kenya.
Afr J Lab Med. 2015 Oct 5;4(1):137. doi: 10.4102/ajlm.v4i1.137. eCollection 2015.
A key objective in basic research on human African trypanosomiasis (HAT) is developing a cheap and reliable experimental model of the disease for use in pathogenesis and drug studies.
With a view to improving current models, a study was undertaken to characterise the virulence and pathogenicity of three stabilates, labelled as International Livestock Research Institute (ILRI)-2918, ILRI-3953, and Institute of Primate Research (IPR)-001, infected into Swiss white mice.
Swiss white mice were infected intraperitoneally with trypanosomes and observed for parasitaemia using wet blood smears obtained by tail snipping. Induction of late-stage disease was undertaken using diminazene aceturate (40 mg/kg, Berenil) with curative treatment done using melarsoprol (3.6 mg/kg, Arsobal).
The prepatent period for the stabilates ranged from three to four days with mean peak parasitaemia ranging from Log 6.40 to 8.36. First peak parasitaemia for all stabilates varied between six and seven days post infection (DPI) followed by secondary latency in ILRI-2918 (15-17 DPI) and IPR-001 (17-19 DPI). Survival times ranged from six DPI (ILRI-3953) to 86 DPI (IPR-001). Hindleg paresis was observed in both ILRI-3953 (at peak parasitaemia) and ILRI-2918 (after relapse parasitaemia). Mice infected with IPR-001 survived until 54 DPI when curative treatment was undertaken.
This study demonstrated that the stabilates ILRI-2918 and ILRI-3953 were unsuitable for modelling late-stage HAT in mice. The stabilate IPR-001 demonstrated the potential to induce chronic trypanosomiasis in Swiss white mice for use in development of a late-stage model of HAT.
人类非洲锥虫病（HAT）基础研究的一个关键目标是开发一种廉价且可靠的疾病实验模型，用于发病机制和药物研究。
为改进现有模型，开展了一项研究，以表征感染瑞士小白鼠的三种保种培养物（分别标记为国际家畜研究所（ILRI）-2918、ILRI-3953和灵长类动物研究所（IPR）-001）的毒力和致病性。
将锥虫经腹腔注射感染瑞士小白鼠，通过剪尾获取湿血涂片观察寄生虫血症。使用乙酰甘氨酸二脒那嗪（40mg/kg，贝尼尔）诱导晚期疾病，并使用美拉胂醇（3.6mg/kg，砷苯甘胺）进行治疗。
保种培养物的潜伏期为3至4天，平均寄生虫血症峰值范围为Log 6.40至8.36。所有保种培养物的首次寄生虫血症峰值在感染后6至7天之间出现，随后ILRI-2918（15 - 17天）和IPR-001（17 - 19天）出现二次潜伏期。存活时间从6天（ILRI-3953）到86天（IPR-001）不等。在ILRI-3953（在寄生虫血症峰值时）和ILRI-2918（复发寄生虫血症后）均观察到后肢麻痹。感染IPR-001的小鼠在进行治疗性治疗时存活至54天。
本研究表明，保种培养物ILRI-2918和ILRI-3953不适用于在小鼠中模拟晚期HAT。保种培养物IPR-001显示出在瑞士小白鼠中诱导慢性锥虫病以用于开发晚期HAT模型的潜力。
