Transmission of <i>Leishmania donovani</i> in the Hills of Eastern Nepal, an Outbreak Investigation in Okhaldhunga and Bhojpur Districts

Background In the Indian subcontinent, Visceral leishmaniasis is endemic in a geographical area coinciding with the Lower Gangetic Plain, at low altitude. VL occurring in residents of hill districts is therefore often considered the result of Leishmania donovani infection during travel. Early 2014 we conducted an outbreak investigation in Okhaldhunga and Bhojpur districts in the Nepal hills where increasing number of VL cases have been reported. Methodology/Principal Findings A house-to-house survey in six villages documented retrospectively 35 cases of Visceral Leishmaniasis (VL). Anti-Leishmania antibodies were found in 22/23 past-VL cases, in 40/416 (9.6%) persons without VL and in 12/155 (7.7%) domestic animals. An age- and sex- matched case-control study showed that exposure to known VL-endemic regions was no risk factor for VL, but having a VL case in the neighbourhood was. SSU-rDNA PCR for Leishmania sp. was positive in 24 (5%) of the human, in 18 (12%) of the animal samples and in 16 (14%) bloodfed female Phlebotomus argentipes sand flies. L. donovani was confirmed in two asymptomatic individuals and in one sand fly through hsp70-based sequencing. Conclusions/Significance This is epidemiological and entomological evidence for ongoing local transmission of L. donovani in villages at an altitude above 600 meters in Nepal, in districts considered hitherto non-endemic for VL. The VL Elimination Initiative in Nepal should therefore consider extending its surveillance and control activities in order to assure VL elimination, and the risk map for VL should be redesigned.背景 在印度次大陆，内脏利什曼病（Visceral leishmaniasis, VL）在低海拔的恒河下游平原地区呈地方性流行态势。因此，山地居民罹患的VL通常被认为是旅行期间感染杜氏利什曼原虫（Leishmania donovani）所致。2014年初，我们在尼泊尔山区的奥克塔尔敦加（Okhaldhunga）与博杰普尔（Bhojpur）县开展暴发调查，该两县此前报告的VL病例数呈持续上升趋势。 方法与主要结果 对6个村庄开展逐户调查，回顾性确认了35例内脏利什曼病（VL）病例。对23例既往VL病例的检测显示，22例可检出抗利什曼原虫抗体；在416名无VL病史的人群中，40人（9.6%）抗体检测呈阳性；在155只家养动物中，12只（7.7%）抗体检测呈阳性。随后开展的年龄与性别匹配的病例对照研究显示，暴露于已知VL流行区并非VL的危险因素，但邻里存在VL病例则为独立危险因素。针对利什曼原虫小亚基核糖体DNA（SSU-rDNA）的聚合酶链式反应（PCR）检测结果显示，5%的人类样本（24份）、12%的动物样本（18份）以及14%的吸血雌性银足白蛉（Phlebotomus argentipes，16只）呈阳性。通过基于热休克蛋白70（hsp70）的测序分析，我们在2名无症状个体与1只白蛉样本中确认了杜氏利什曼原虫（L. donovani）。 结论与意义 本研究提供了流行病学与昆虫学证据，证实杜氏利什曼原虫在尼泊尔海拔600米以上的村庄中存在持续本地传播，而此类地区此前被认为不属于VL流行区。因此，尼泊尔的VL消除倡议应考虑扩大监测与防控活动范围，以确保实现VL消除目标，同时需重新修订VL流行风险地图。