Visceral leishmaniasis: An immunological viewpoint on asymptomatic infections and post kala azar dermal leishmaniasis

Elimination of visceral leishmaniasis is a priority programme in Indian subcontinent.The World Health Organization has set a new target to eliminate kala-azar by the year 2020 as previous target elimination year(2015) has passed.The elimination programme has successfully curbed the rate of infection in endemic regions; however, there are still few challenges in its route.The current drug control regime is extremely limited and comprises only two(amphotericin B and miltefosine) drugs, which are also susceptible for parasites resistance.Moreover, these drugs do not produce sterile cure, and cured patients may develop post kala-azar dermal leishmaniasis even after a decade of cure leaving behind a potent source of parasitic reservoirs for further disease transmission.A significant proportion of endemic population remain seropositive but aymptomatic for many years without any clinical symptom that serve as latent parasitic reservoirs.The lack of tools to identify live parasites in asymptomatic infections and there association in disease transmission, parameters of sterile cure along with post kala-azar dermal leishmaniasis progression remain a major threat in its elimination.In this review, we discuss the potential of host immune inhibitory mechanisms to identify immune correlates of protective immunity to understand the mystery of asymptomatic infections, sterile cure and post kala azar dermal leishmaniasis.

Choice of providers for treating a neglected tropical disease:an empirical analysis of kala azar in Nepal

Objective:To examine the choice of healthcare providers for treating kala azar(KA) in Nepal. Methods:Information was collected from clinically diagnosed KA patients seeking care from public hospitals located in KA endemic districts.The survey collected information from more than 25 percent of total KA cases in the country.For empirical estimation of probability of choosing a provider-type as a first contact healthcare provider,a multinomial logit model was defined with five alternative options with self care as the reference category.Results:The empirical model found that price of medical care services,income of households,knowledge of patients on KA and KA treatment,borrowing money,age of patient,perceived quality of provider types,etc.determine the likelihood of seeking care from the alternative options considered in the analysis.All variables have expected signs and are con.vstent with earlier studies.The price and income elasticity were found to be very high indicating that poorer households are very sensitive to price and income changes,even for a severe disease like KA.Using the empirical models, we have analyzed two policy instruments:demand side financing and interventions to improve the knowledge index about KA.Conclusions:Due to high price elasticity of KA care and high spillover effects of KA on the society,policy makers may consider demand side financing as an instrument to encourage utilization of public hospitals.

Relative abundance of Phlebotominae sandflies with emphasis on vectors of kala-azar

Objective:To identify potential vectors of kala-azar from Northern plains of Uttar Pradesh, India.Methods:The collections were made using sticky paper traps,CDC light-traps,and aspirators from outdoors as well as indoors.All female sandflies were dissected and identified. Results:During January 2009 to July 2009,528 phlebotomine specimens were collected including 329 males(62.3%) and 199 females(37.7%),approximately 238(45%) of them were captured from indoor and 290(55%) from outdoor resting places.Five species belonging to the genera Phlebotomus(8%) and Sergentomyia(92%) were recorded.Conclusions:Public health measures such as case detection and treatment,the control of sandflies,the conjunction elimination of infected stray dogs and health education can be effective in controlling the disease.

Jaundice in pediatric visceral leishmaniasis (kala-azar) patients

Objective:Visceral leishmaniasis(Kala-azar) is endemic in many countries including Bangladesh.Clinical presentation of visceral leishmaniasis in children and adult may vary and at time may simulate many tropical and hepatobiliary diseases.Jaundice and ascites are not common in kala-azar patients.Methods:During the period of January 2005 to December 2006,all the records of the confirmed kala-azar patients presented with jaundice were included in this study.Kala-azar was confirmed by serology test ICT(Immuno Chromatography) and Bone Marrow study.Results:Total 12 kala-azar patients were encountered during this period.Among these twelve cases,presenting features were jaundice(7),splenomegaly(12),hepatomegaly(11) and ascites (4).Initial clinical diagnosis of chronic liver disease(CLD) was made in(5),Congenital hemolytic anaemia in(1) and kala-azar in rest of the patients(6 ).Common leucopenia and relative lymphocytosis was not observed in any patients.Conclusion:Kala-azar may present with various clinical manifestation in children and adult.Jaundice can be considered to be a common manifestation particularly in pediatric kala-azar patients.Otherwise,it may mislead to another diagnosis if it is taken as a rare feature in kala-azar.

Prevalence of kala-azar infection in Pokot county, Amudat district, Northeastern Uganda

Introduction: Visceral leishmaniasis (kala-azar) caused by Leishmania donovani and transmitted by the sand-fly Phlebotomus martini is endemic in certain foci in north-eastern Uganda where it is thought to be confined to Pokot county, Amudat district. Amudat hospital records (April 1998-March 1999) indicated that kala-azar accounted for about 17% of hospital in-patients. However the actual prevalence of kala-azar infection in the community in Pokot county is unknown. This lack of information limits efforts geared towards its control. Objective: To determine the prevalence of kala-azar infection in Pokot county. Methods: A cross-sectional study was conducted in Pokot county in March 2010. The study participants were ≥ 5 years and were randomly selected from the age and sex strata in the chosen clusters. A questionnaire that elicited demographic profiles of participants was used for data collection. Standard procedure for direct agglutination test using blood samples collected from participants on blotting papers was performed. Data was entered in EPIINFO 3.3 and exported to STATA 10, where descriptive statistics were generated. Results: The overall prevalence of kala-azar infection in Pokot county was 17.2% but the prevalence of symptomatic infection in the community was 2.5%. The ratio of symptomatic to asymptomatic kala-azar was 1:6. Loroo sub-county had the highest prevalence of kala-azar infection followed by Karita and Amudat sub-counties at 31.9%, 14.6% and 5.3%, respectively. Conclusion: With kala-azar infection prevalence at 17.2% in the community, there is an urgent need to institute control program spearheaded by ministry of health, in the region. Furthermore, recent reports of cases from other districts within the region, the heterogeneous distribution of infection within the county and the current risk factors, including the role of animals in kala-azar transmission in this area need to be evaluated.

《黑热病诊疗方案(2023年版)》解读

黑热病是所有寄生虫病中的第三大常见发病原因,死亡率仅次于疟疾。在亚洲地区,通过媒介的控制、诊断及治疗手段的提高,发病率在减少,但在东非地区,病例数仍在持续增加。由于疾病表现形式的千变万化,寻求新的诊断工具、开发新的治疗方法,将是未来黑热病的重点研究方向。本文对照2023年黑热病诊疗方案的重点内容进行解读,同时结合最近相关文献,以期帮助国内医疗人员更好的管理和救治黑热病患者。

Decision-making process of Kala Azar care: results from a qualitative study carried out in disease endemic areas of Nepal

Background:Analysis of consumer decision making in the health sector is a complex process of comparing feasible alternatives and evaluating the levels of satisfaction associated with the relevant options.This paper makes an attempt to understand how and why consumers make specific decisions,what motivates them to adopt a specific health intervention,and what features they find attractive in each of the options.Method:The study used a descriptive-explanatory design to analyze the factors determining the choices of healthcare providers.Information was collected through focus group discussions and in-depth interviews.Results:The results suggest that the decision making related to seeking healthcare for Kala Azar(KA)treatment is a complex,interactive process.Patients and family members follow a well-defined road map for decision making.The process of decision making starts from the recognition of healthcare needs and is then modified by a number of other factors,such as indigenous knowledge,healthcare alternatives,and available resources.Household and individual characteristics also play important roles in facilitating the process of decision making.The results from the group discussions and in-depth interviews are consistent with the idea that KA patients and family members follow the rational approach of weighing the costs against the benefits of using specific types of medical care.Conclusion:The process of decision making related to seeking healthcare follows a complex set of steps and many of the potential factors affect the decision making in a non-linear fashion.Our analysis suggests that it is possible to derive a generalized road map of the decision-making process starting from the recognition of healthcare needs,and then modifying it to show the influences of indigenous knowledge,healthcare alternatives,and available resources.

宏基因组二代测序技术诊断骨髓涂片阴性婴幼儿黑热病3例报告

目的对3例骨髓涂片阴性黑热病患儿的病原学宏基因组二代测序技术(mNGS)检测结果进行分析,探讨mNGS在临床的应用价值。方法回顾性分析2021年4月至2022年2月PICU收集的3例骨髓涂片阴性患儿黑热病的临床资料。结果3例患儿中女2例,男1例,年龄均<3岁。均有发热,骨髓涂片均阴性,外周血mNGS检测均提示利什曼原虫感染,且未见其他病原感染,经葡萄糖酸锑治疗后均治愈。结论骨髓涂片阴性的婴幼儿黑热病早期诊断困难。对于临床感染性疾病,尤其是常规检测无法确定病原的疑难危重的感染性疾病,mNGS能提供快速准确的病原学诊断支持,助力精准诊治。

荒漠型杜氏利什曼原虫虫株在体内外的致病力及保存方法研究

目的通过动物攻毒实验观察荒漠型杜氏利什曼原虫虫株在动物体内外的致病力,探索保持该虫株致病力的保存方法。方法将从rK39抗体阳性灰仓鼠脾脏中分离获得的荒漠型杜氏利什曼原虫虫株分别在体外培养基中传代培养至7 d、30 d、36 d、44 d、60 d、90 d和150 d后,按2.6×10^(5)条/只剂量腹腔接种至草原兔尾鼠,接种后60 d计算动物的脾脏系数、虫株感染率和抗体阳性率。进一步将荒漠型杜氏利什曼原虫虫株分别接种灰仓鼠和草原兔尾鼠进行传代保种,比较两种动物感染该虫株后的存活时间和致病力变化。结果体外培养7~150 d的荒漠型杜氏利什曼原虫虫株接种后,草原兔尾鼠的脾脏系数由7 d的1.0%上升至30 d的2.2%,达到正常脾脏系数(0.15%)的10倍以上,而60 d的脾脏系数虽有下降,但仍然达正常值的3倍;虫株感染率和抗体阳性率由7 d的80%逐步下降至60 d的0%;90 d时的各项观测指标与对照组相比无明显差异,均在正常值范围内。传代感染虫株后,草原兔尾鼠的存活时间为1~13个月,感染的半数个体于接种后4个月内死亡;而灰仓鼠的存活时间为5~31个月,感染的半数个体于接种后13.7个月内死亡;两种动物的平均死亡时间差异显著(t=0.0001,P<0.001),脾脏系数差异无统计学意义(t=0.990,P>0.05)。该虫株在两种动物体内的致病力一致,且在动物体内连续传代4年仍然具有致病力。结论荒漠型杜氏利什曼原虫虫株随体外培养时间延长,其致病力逐步降低,90 d时对草原兔尾鼠已无致病力,说明培养基传代培养方法不能保持该虫株对动物的致病力。动物体内传代接种才可以保持该虫株对动物的致病力。

Emerging leishmaniasis in southern Himalayas:A mini-review

Leishmaniasis is a vector-borne parasitic disease affecting millions of people worldwide.However,in the last decade,the number of cases has been reduced from well-documented endemic parts,but sporadic cases have been reported widely from various non-endemic areas,especially from the southern Himalayan zone.This raises concerns about the emergence of new ecological niches.This warrants a critical evaluation of key factors causing this rapid spread and possibly indigenous transmission.This mini-review article is aimed to briefly address the parasite,the vector,and the environmental aspects in the transmission of leishmaniasis in these new foci against a background of worldwide endemic leishmaniasis with a special focus on the southern Himalayan zone.As the lack of knowledge about the causative parasites,vectors,reservoir hosts,atypical presentations,and their management make the problem serious and may lead to the emergence of public health issues.The present works also reviewed the existing information regarding clinical variations,diagnostic methods,treatment,its outcome,and ignite for further research in these aspects of the disease.

基于环境要素的民国时期黑热病流行危险分区

黑热病是一种新传入的慢性地方性传染病,在部分地区曾造成深远影响.该文综合运用Grapher时序分析、GIS空间分析、MaxEnt生态位分析等方法,探讨民国时期黑热病流行的时空特征、危险分区及影响因素,结果表明:1)民国时期,黑热病的流行频度为78.95%,集中流行于夏、秋季,并分别在1923年、1934—1937年、1946年形成流行高峰期.2)民国时期,黑热病几乎全部分布于长江以北地区,并在苏、皖、豫、鲁4省交界地带形成密集分布区.3)黑热病“长江北、类圈层”的适生范围,奠定了黑热病危险等级的地理格局,表现为黄河中下游及淮河流域省份危险等级高,尤其是特危等级的江苏(含上海)、安徽、河南、山东和高危等级的河北(含北京、天津)、山西、陕西等省份.4)黑热病流行的影响因素中,河网密度(20.2%)、日照时数(17.3%)、海拔高程(14.5%)、最低气温(10.0%)等因素的贡献度最高.

1例儿童耐锑剂黑热病治疗分析并文献复习

目的:探讨两性霉素B脂质体治疗儿童耐锑剂黑热病的有效性及安全性。方法:回顾性分析1例耐锑剂黑热病患儿给予两性霉素B脂质体治疗的病例资料,并进行相关文献复习。结果:患儿,女,1岁10个月,主因“间断发热伴脾大1年余”入院。生后10个月首次发病,表现为高热、贫血、肝脾肿大,抗感染效果欠佳,骨髓细胞学检查确诊黑热病,予多次锑剂治疗,出现复发及锑剂耐药,给予两性霉素B脂质体治疗,监测外周血及骨髓微生物宏基因组测序利什曼原虫转阴,获得临床及病原学治愈,目前随访8个月未见复发。结论:两性霉素B脂质体可治疗儿童耐锑剂黑热病,安全有效,不良反应少。

黑热病482例骨髓象分析

目的观察黑热病患者骨髓象变化。方法选取陇南市第一人民医院1990年7月-2021年9月有完整的骨髓报告单的初发黑热病病例共计482例,对其骨髓象进行分析。结果杜氏利什曼原虫检出率为76.56%,原虫密度“+”者占51.77%;“++”者占15.04%。骨髓增生程度,活跃者占87.34%;粒系增生活跃占64.52%;红系增生活跃占85.68%;淋巴细胞系>20%者占31.33%;浆细胞≥3.0%者占8.09%。单张骨髓涂片巨核细胞>7个者占87.67%。结论黑热病骨髓利什曼原虫检出率较高,是诊断黑热病的重要方法,阳性者原虫密度以“+”“++”者为主。骨髓以增生活跃为主,粒系、红系增生活跃,可伴浆细胞增多,可伴噬血细胞增多,巨核细胞增生活跃。

绥德县畜间黑热病综合防治调研

黑热病(Kala-azar)亦称内脏利什曼病(Visceral leishmaniasis),是一种严重的人畜共患传染病。近年来,绥德县陆续发生了几起人患黑热病的病例,追溯历史上黑热病在人、畜间的发生情况,绥德县广大医护人员和畜牧兽医从业人员经过深入流调监测,分析该病发生原因,提出今后黑热病综合预防控制的建议。

新疆喀什地区黑热病暴发的危险因素分析

目的探讨新疆喀什地区黑热病暴发流行的危险因素。方法采用病例对照研究,自制调查问卷,以基于利什曼原虫kDNA保守区PCR扩增的分子方法检测呈阳性感染的为病例组,按1∶3匹配选择年龄、性别、营养状况、职业、家庭收入与消费、受教育程度等方面差别无统计学意义(P>0.05),且利什曼原虫感染检测呈阴性的健康人为对照组,对性别、环境和行为等10个潜在危险因素进行单因素和多因素logistic回归分析。结果75份易感人血样感染利什曼原虫阳性率为82.67%(62/75)。单因素分析显示:户外被叮咬、户外露宿习惯、邻居有黑热病患者、蚊帐及趋避剂杀虫剂的使用与当地易感人群感染利什曼原虫关系密切,危险比(RH)值和95%可信区间(95%CI)依次为7.296,(3.102,1.16)、15.429(5.876,8.995)、75.6(26.6,214.9)、0.311(0.132,0.733)、0.491(0.292,0.672);多因素分析显示:户外被叮咬、邻居有黑热病患者是感染利什曼原虫的危险因素,使用蚊帐是保护性因素,RH值和95%CI为12.56(3.476,45.38)、140.987(37.59,528.8)、0.185(0.05,0.68)。结论在该地区易感人群感染利什曼原虫率较高的情况下,对当地居民普及黑热病的危害及防御措施,及时确诊并彻底诊治黑热病患者,尽量避免户外被叮咬,养成使用蚊帐习惯是预防控制当地人源型黑热病感染暴发的有效措施。

湖北省黑热病流行态势的评估

[目的 ]复查湖北省自 1989年起陆续报告的 14例“黑热病”,及评估我省黑热病的流行现况。 [方法 ]复查“黑热病”患者的骨髓片、免疫学检查 (L DT、IFAT)、接种动物及真菌培养、媒介 (白蛉 )和保虫宿主 (犬 )的调查。[结果 ]除 1例输入的和 1例残存的皮肤型黑热病外 ,其余 12例为播散型荚膜组织胞浆菌病。1997～ 1999年在 9个地市的 2 3个县 (市 )的 2 5个乡镇进行了免疫学监测 ,对 13 890人采用利什曼素皮内试验 (L DT) ,阳性率 0 .0 0 7% ,40岁以下的人群无阳性。其中 175 6人作间接荧光抗体试验 (IFAT) ,结果均为阴性。在调查区内未发现中华白蛉。查犬 30 2只 ,未发现病犬。 [结论 ]湖北省已消灭黑热病 。

137例内脏利什曼病患者临床分析

目的分析近十几年四川地区内脏利什曼病住院患者临床和流行病学特征。方法收集2000年1月至2012年4月四川大学华西医院收治的内脏利什曼病患者137例的资料,回顾性分析流行病学、临床特点、治疗和转归。结果137例患者中,64.2%(88/137)居住在四川及周边内脏利什曼病流行区,35.8%(49/137)有流行区逗留史。137例中,农村占84.7%(116/137),城镇占15.3%(21/137)。临床表现以发热,肝、脾及淋巴结肿大,全血细胞减少和球蛋白明显增高为主。137例患者利什曼原虫rk39抗体试纸条检测均为阳性。诊断明确者用葡萄糖酸锑钠治疗,治愈118例(86.1%),脾切除4例(2.9%),复发9例(6.6%)。137例中首诊疑诊为内脏利什曼病者105例,误诊率为23.4%(32/137)。结论关注流行病学史、检测rk39抗体,以及尽早骨髓涂片或组织活检有助于早期诊治,葡萄糖酸锑钠疗效较好。

新发现的内脏利什曼病流行区新疆民丰县Ⅰ．流行病学调查

目的对新疆民丰县一个新发现的内脏利什曼病(黑热病)流行区进行现场流行病学调查。方法2007年6月采用回顾性调查和现况调查相结合,对民丰县安迪尔乡所有居民进行逐户入户调查。内容包括家庭成员中20年来的健康状况、既往有无疑似内脏利什曼病史(包括已过世者),并对15岁以下儿童进行体查(触诊肝、脾);对部分居民进行利什曼素皮内试验和rk39免疫层析试条检测。结果共调查居民313人,未见现症病例。既往有疑似内脏利什曼病史者60例,其中13例已过世。171人进行利什曼素皮内试验检测,阳性率为99.4%(170/171),其中有疑似内脏利什曼病病史者的阳性率为96.6%(28/29)。197人进行rk39免疫层析试条检测,阳性率为10.2%(20/197),其中有疑似内脏利什曼病史者的阳性率为19.4%(6/31),追溯诊断为既往内脏利什曼病病例。结论新疆民丰县为内脏利什曼病流行区。

新发现的内脏利什曼病流行区新疆民丰县Ⅱ．传播媒介的初步研究

目的在新发现的流行区新疆塔里木盆地南缘民丰县调查内脏利什曼病(黑热病)的媒介蛉种。方法在民丰县安迪尔乡雅通古斯村居民点和附近野外采集白蛉,经鉴定后计算蛉种组成和数量比例;定人、定点、定时观察白蛉数量统计密度;观察白蛉昼夜活动的数量变动;解剖白蛉,分析雌蛉生殖营养周期;检查白蛉有无前鞭毛体自然感染。结果捕获白蛉1210只,其中99.17%(1200/1210)为吴氏白蛉;6月上中旬是该蛉季节消长的第一高峰;生殖营养周期分析表明吴氏白蛉为野生野栖蛉种,夜间活动的白蛉主要在户外吸血,有较强的亲人性;在2只白蛉体内查到自然感染前鞭毛体。结论塔里木盆地南缘民丰县安迪尔乡雅通古斯村存在内脏利什曼病传播媒介吴氏白蛉,并有利什曼前鞭毛体自然感染,表明当地存在内脏利什曼病自然疫源地。

河南黑热病媒介白蛉调查

目的：掌握我省基本消灭黑热病后传播媒介白蛉的残存情况。方法：在有代表性地区采用人工捕捉白蛉，解剖鉴定蛉种。结果：在河南京广铁路以西丘陵、山区媒介中华白蛉持续存在，如有病例输入，黑热病仍有潜在传播的危险；在铁路以东平原地区，白蛉基本绝迹，即使有病例输入，也似无潜伏期传播的危险。