2018年 · 第07卷第03期

Neglected tropical diseases (NTDs) are closely related to poverty and affect over a billion people in developing countries. The unmet treatment needs cause high mortality and disability thereby imposing a huge burden with severe social and economic consequences. Although coordinated by the World Health Organization, various philanthropic organizations, national governments and the pharmaceutical industry have been making efforts in improving the situation, the control of NTDs is still inadequate and extremely difficult today. The lack of safe, effective and affordable medicines is a key contributing factor. This paper reviews the recent advances and some of the challenges that we are facing in the fight against NTDs.

In recent years, a number of innovations have demonstrated propensity to promote drug discovery and development for NTDs. Implementation of multilateral collaborations leads to continued efforts and plays a crucial role in drug discovery. Proactive approaches and advanced technologies are urgently needed in drug innovation for NTDs. However, the control and elimination of NTDs remain a formidable task as it requires persistent international cooperation to make sustainable progresses for a long period of time. Some currently employed strategies were proposed and verified to be successful, which involve both mechanisms of 'Push' which aims at cutting the cost of research and development for industry and 'Pull' which aims at increasing market attractiveness. Coupled to this effort should be the exercise of shared responsibility globally to reduce risks, overcome obstacles and maximize benefits. Since NTDs are closely associated with poverty, it is absolutely essential that the stakeholders take concerted and long-term measures to meet multifaceted challenges by alleviating extreme poverty, strengthening social intervention, adapting climate changes, providing effective monitoring and ensuring timely delivery.

The ongoing endeavor at the global scale will ultimately benefit the patients, the countries they are living and, hopefully, the manufacturers who provide new preventive, diagnostic and therapeutic products.

Leptospirosis morbidity and mortality rates in China have decreased since the 2000s. Further analyses of the spatiotemporal and demographic changes occurring in the last decade and its implication on estimates of disease burden are required to inform intervention strategies. In this study, we quantified the epidemiological shift and geographical heterogeneity in the burden of leptospirosis during 2005-2015 in China.

We used reported leptospirosis case data from 1st January 2005 to 31st of December 2015 that routinely collected by the China Information System for Disease Control and Prevention (CISDCP) to analyze the epidemiological trend and estimate the burden in terms of disability-adjusted life-years (DALYs) over space, time, and demographical groups.

A total of 7763 cases were reported during 2005-2015. Of which, 2403 (31%) cases were the laboratory-confirmed case. Since 2005, the notified incidence rate was gradually decreased (P < 0.05) and it was relatively stable during 2011-2015 (P> 0.05). During 2005-2015, we estimated a total of 10313 DALYs were lost due to leptospirosis comprising a total of 1804 years-lived with disability (YLDs) and 8509 years-life lost (YLLs). Males had the highest burden of disease (7149 DALYs) compared to females (3164 DALYs). The highest burden estimate was attributed to younger individuals aged 10-19 years who lived in southern provinces of China. During 2005-2015, this age group contributed to approximately 3078 DALYs corresponding to 30% of the total DALYs lost in China. Yet, our analysis indicated a declining trend in burden estimates (P< 0.001) since 2005 and remained relatively low during 2011-2015. Low burden estimates have been identified in the endemic regions where infections principally distributed. Most of the changes in DALY estimates were driven by changes in YLLs.

In the last 11-years, the burden estimates of leptospirosis have shown a declining trend across the country; however, leptospirosis should not be neglected as it remains an important zoonotic disease and potentially affecting the young and productive population in economically less-developed provinces in southern of China. In addition, while in the last five years the incidence has been reported at very low-level, this might not reflect the true incidence of leptospirosis. Strengthened surveillance in the endemic regions is, hence, substantially required to capture the actual prevalence to better control leptospirosis in China.

Bacterial diarrhea is one of the most common causes for medical consultations, mortality and morbidity in the world. Diarrheagenic Escherichia coli (DEC) and non-typhoidal Salmonella (NTS) are major intestinal pathogens in developing countries, and the indiscriminate use of antibiotics has greatly contributed to resistant strains. Hence, the aim of the present study is to identify the antimicrobial resistance patterns and the molecular characteristics of DEC and NTS in southwest, China.

1121 diarrheal patients and 319 non-diarrheal subjects across all age groups were recruited from four sentinel hospitals from June 2014 to July 2015 in Kunming City, Yunnan Province. Each stool specimen was collected to detect DEC and NTS with standard microbiological and molecular methods. Antimicrobial resistance testing was performed with the Kirby-Bauer disk diffusion method, and the standards for antimicrobial susceptibility testing complied with the Clinical and Laboratory Standards Institute (CLSI). Molecular characterization of strains was carried out using pulsed-field gel electrophoresis (PFGE). A structured questionnaire was used to record basic epidemiological data (e.g. sex, age, residence, season, etc.). Data were analyzed using Chi-square or Fisher's exact test. (Continued on next page)

DEC was detected in 127 (11.33%) diarrhea cases and 9 (2.82%) non-diarrheal cases (χ² = 20.69, P < 0.001, OR = 4.36, 95% CI: 2.19–8.65), and the prevalence of NTS isolated from diarrhea cases was higher than that of non-diarrheal cases across all age groups (n = 42, 3.75%, n = 1, 0.31%, χ² = 10.10, P = 0.002, OR = 12.38, 95% CI: 1.70–90.29). The rates of resistance to ten antibiotics of DEC and NTS showed significant differences (χ² = 386.77, P < 0.001; χ² = 191.16, P < 0.001). The rates of resistance to Amoxicillin and Clavulafiate (AMC), Cephalothin (CEP), Gentamicin (GEN) and Sulfamethoxazole-Trimethoprim (SXT) of DEC isolated from diarrhea cases were higher than those of NTS isolated from diarrhea patients (37.01% vs 14.29%, χ²= 7.57, P= 0.006; 29.92% vs 11.90%, χ² = 5.40, P = 0.02; 37.01% vs 11.90%, χ² = 5.80, P = 0.016; 62.20% vs 26.19%, χ² = 16.44, P < 0.001; respectively). Ciprofloxacin (CIP) was the most sensitive antibiotic for DEC and NTS strains isolated from diarrhea cases. Resistance rates of DEC isolates from cases and controls to more than three kinds antimicrobials (multidrug resistance, MDR) showed no significant differences (81.10% vs 88.89%, P= 0.33). Pulsotype patterns of DEC strains were highly diverse; however, the pulsotype pattern of NTS strains was closely related to the serotype. The pattern of S. enteritidis was highly similar, but the S. enterica Typhimurium strain was discrete.

Antibiotic resistance of Enterobacteriaceae is of great concern. The societal effects of antibiotic use justify strict monitoring to combat increases in antimicrobial resistance. Molecular epidemiology and systematic epidemiological investigation can provide accurate evidence for tracking the infection source.

Fever remains a major public health problem. In Burkina Faso, more than half of febrile children are considered not to be infected by malaria. This study prospectively assessed probable (treatable) causes of fever in Burkinabe children.

A prospective study was conducted among febrile children (≥37.5 °C) under 5 years of age presenting at four health facilities and one referral hospital in rural Burkina Faso. From each participant, blood was collected for malaria microscopy and culture, urine for dipstick testing and culturing if tested positive for leucocytes and nitrite, stool for rotavirus/adenovirus testing, culture and parasitology, and a nasopharyngeal swab for culture.

In total 684 febrile children were included in the study. Plasmodium falciparum malaria was found in 49.7% (340/684) of the participants and non-malaria infections in 49.1% (336/684) of children. The non-nalaria infections included gastro-intestinal infections (37.0%), common bacterial pathogens of nasopharynx (24.3%), bacterial bloodstream infections (6.0%) and urinary tract infections (1.8%). Nearly 45% (154/340) of the malaria infected children were co-infected with non-nalaria infections, but only 3.2% (11/340) of these co-infections could be considered as a possible alternative cause of fever. In contrast, in the malaria microscopy negative children 18.0% (62/344) of the infections could be the probable cause of the fever. Pathogens were not isolated from 23.7% (162/684) of the febrile cases.

Malaria remains the most common pathogen found in febrile children in Burkina Faso. However, a relative high number of febrile children had non-malaria infections. The correct diagnosis of these non-malaria fevers is a major concern, and there is an urgent need to develop more point-of-care diagnostic tests and capacities to identify and treat the causes of these fevers.

Lymphatic filariasis (LF) is endemic in Myanmar and targeted for elimination. To highlight the National Programme to Eliminate Lymphatic Filariasis (NPELF) progress between 2000 and 2014, this paper describes the geographical distribution of LF, the scale-up and impact of mass drug administration (MDA) implementation, and the first evidence of the decline in transmission in five districts.

The LF distribution was determined by mapping historical and baseline prevalence data collected by NPELF. Data on the MDA implementation, reported coverage rates and sentinel site surveillance were summarized. A statistical model was developed from the available prevalence data to predict prevalence at township level by year of measurement. Transmission assessment survey (TAS) methods, measuring antigenemia (Ag) prevalence in children, were used to determine whether prevalence was below a level where recrudescence is unlikely to occur.

The highest baseline LF prevalence was found in the Central Valley region. The MDA implementation activities scaled up to cover 45 districts, representing the majority of the endemic population, with drug coverage rates ranging from 60.0% to 98.5%. Challenges related to drug supply and local conflict were reported, and interrupted MDA in some districts. Overall, significant reductions in LF prevalence were found, especially after the first 2 to 3 rounds of MDA, which was supported by the corresponding model. The TAS activities in five districts found only two Ag positive children, resulting in all districts passing the critical threshold.

Overall, the Myanmar NPELF has made positive steps forward in the elimination of LF despite several challenges, however, it needs to maintain momentum, drawing on international stakeholder support, to aim towards the national and global goals of elimination.

Schistosomiasis is one of the most important neglected tropical diseases. If unrecognised and untreated, the chronic infection can lead to irreversible complications.

Retrospective observational study aimed at describing clinical history, laboratory findings and imaging presentation of imported schistosomiasis diagnosed at the Centre for Tropical Diseases, Sacro Cuore Don Calabria Hospital of Negrar, Verona, Italy from 2010 to 2014. The aim of our study was to assess differences in demographic characteristics, clinical presentation, laboratory data and ultrasound findings between immigrants/visiting friends and relatives (VFR) from endemic countries (endemic group) and expatriates/travellers (non-endemic group).

A total of 272 patients were retrieved: 234 in the endemic and 38 in the non-endemic group. Most of the patients acquired schistosomiasis in Africa (97.4%). Symptoms were reported by 52.9% of the patients; abdominal pain (36%), macroscopic hematuria (11.3%), and genito-urinary symptoms (7.4%) being the most frequently reported. Increased IgE and blood eosinophilia were observed in 169 (63.8%) and 130 (47.8%) patients, respectively. The proportion of positive serology was 250/272 (91.9%).The Circulating Cathodic Antigen CCA for Schistosoma mansoni was positive in 14/61 individuals (23%). At microscopy, infected subjects were 103/272 (37.9%). The species of Schistosoma found were S. haematobium (47.6%), S. mansoni (46.6%) or both (5.8%). Schistosomiasis was classified as confirmed in 103 (37.9%), probable in 165 (60.6%) and suspected in 4 (1.5%) cases using clinical presentation, laboratory data and ultrasound findings. The infection was further classified based on organ involvement: intestinal (17.9%), hepatosplenic (5.1%), urogenital (48.9%), and indeterminate (43.8%). The comparative analysis of endemic and non-endemic patients highlighted differences in sex and age. Endemic patients had more frequent ova identification (41.9% vs. 13.2%, P < 0.001) and increased IgE (70% vs. 26.3%, P < 0.001) when compared with non-endemic. Multivariate analyses showed that younger age, abnormal ultrasound findings and blood eosinophilia were significantly associated with positive microscopy (OR = 0.94, OR = 2.12, OR = 1.98, respectively).

Symptoms, eosinophilia and abnormal ultrasound findings were present in about half of patients, without differences between groups. Many patients had positive serology but negative microscopy, indicating that schistosomiasis might be misdiagnosed. A combination of diagnostic tools may facilitate the diagnosis.

Unmanned aerial vehicles (UAVs) have become useful tools to extend human abilities and capacities. Currently UAVs are being used for the surveillance of environmental factors related to the transmission of infectious diseases. They have also been used for delivering therapeutic drugs and life-saving supplies to patients or isolated persons in extreme conditions. There have been very few applications of UAVs for disease surveillance, control and prevention to date. However, we foresee many uses for these machines in the fight against zoonotic disease. The control of zoonoses has been a big challenge as these diseases are naturally maintained in animal populations. Among 868 reported zoonoses, echinococcosis (hydatid disease) is one of the most severe public health problems and listed as one of 17 neglected tropical diseases targeted for control by the World Health Organization. Infected dogs (domestic or stray) play the most important role as definitive hosts in maintaining the transmission of echinococcosis. However, the actual contribution of wild canines to transmission has received little attention as yet, but should certainly not be ignored. This paper summarizes the history of development and application of UAVs, with an emphasis on their potential use for zoonosis control. As an example, we outline a pilot trial of echinococcosis control in the Qinghai-Tibet Plateau region, in which UAVs were used to deliver baits with praziquantel for wildlife deworming. The data suggested that this is a cost-effective and efficient approach to the control of zoonotic diseases transmitted among wild animal populations.

Ranked among the world's dirtiest countries, Ghana has poor environmental sanitation and hygiene, and a lack of potable water, all of which combined have been largely blamed as the underscoring reasons for cholera outbreaks. The country has concomitantly suffered seasonal cholera outbreaks that have impacted negatively on the population's health, as well as on the nation's economy. To prevent cyclical cholera outbreaks in Ghana, this commentary discusses the associated problems and makes recommendations to solve them.

This commentary aims to throw light on the menace of cholera in Ghana and the need to curb the recurrence of outbreaks and bouts of this epidemic. Response measures, challenges, and lessons learnt from the most recent cholera outbreak are critically assessed to determine how best this public health issue could be resolved. General and specific policy recommendations are identified in this regard.

To resolve this problem, there is a need for an oral cholera vaccine to be introduced. There is also a need to develop strategies and interventions relating to water, sanitation, and hygiene, to be initiated by the Ministry of Health, with component activities that are culturally tailored to Ghanaian communities. Policy change towards the prevention of outbreaks in Ghana is identified as another requisite.

Dogs play a pivotal role in the transmission of cystic echinococcosis (CE), a zoonosis caused by the tapeworm Echinococcus granulosus. We showed previously that dogs vaccinated with two E. granulosus adult-worm specific proteins, EgM9 and EgM123, emulsified with Freund's adjuvants induced significant protective efficacy in terms of reduction in worm burden and egg production after 45 days post-infection. It was not known whether this protection can be sustained using adjuvants suitable for use in dogs.

Recombinant EgM9 and EgM123 were mixed with Quil A or ISCOMs for vaccinating dogs. After three vaccine injections, all the dogs were orally challenge-infected with 200 000 protoscoleces of E. granulosus. After 45 days of infection, all the dogs were euthanized and necropsied for collecting and counting E. granulosus worms. Immunoglobins, including the IgG subclasses IgG1 and IgG2, were detected in the sera of vaccinated dogs by ELISA. To determine whether the protection efficacy could be maintained after 45 days post-infection, we implemented a longevity trial to count eggs in dog faeces for 170 days after infection.

The dogs vaccinated with EgM9 and EgM123 mixed with Quil A and ISCOMs showed similar protective efficacy as the proteins emulsified with Freund's adjuvants in our previous study in terms of reduction of worms and eggs at 45 days post-infection. The longevity trial showed that EgM9 protein-vaccinated group released lower number of eggs per gram compared with the egg counts in the control dogs during the dog trial study.

EgM9 and EgM123 are thus suitable vaccine candidates against E. granulosus infection in dogs.

Brucellosis is a worldwide zoonotic disease caused by Brucella spp. Brucella invades the body through the skin mucosa, digestive tract, and respiratory tract. However, only a few studies on human spontaneous abortion attributable to Brucella have been reported. In this work, the patient living in Shanxi Province in China who had suffered a spontaneous abortion was underwent pathogen detection and Brucella melitensis biovar 3 was identified.

The patient in this study was 22 years old. On July 16, 2015, she was admitted to Shanxi Grand Hospital, Shanxi Province, China because of one day of vaginal bleeding and three days of abdominal distension accompanied by fever after five months of amenorrhea. A serum tube agglutination test for brucellosis and blood culture were positive. At the time of discharge, she was prescribed oral doxycycline (100 mg/dose, twice a day) and rifampicin (600 mg/dose, once daily) for 6 weeks as recommended by the World Health Organization (WHO). No recurrence was observed during the six months of follow-up after the cessation of antibiotic treatment.

This is the first reported case of miscarriage resulting from Brucella melitensis biovar 3 isolated from a pregnant woman who was infected through unpasteurized milk in China. Brucellosis infection was overlooked in the Maternity Hospital because of physician unawareness. Early recognition and prompt treatment of brucellosis infection are crucial for a successful outcome in pregnancy.

Human African trypanosomiasis (HAT) is one of the most complex parasitic diseases known to humankind. It usually occurs in endemic areas in Africa, but is occasionally detected in returning travelers and migrants in non-endemic countries.

In August 2017, a case of HAT was diagnosed in China in a traveler returning from the Masai Mara area in Kenya and the Serengeti area in Tanzania. The traveler visited Africa from 23 July to 5 August, 2017. Upon return to China, she developed a fever (on 8 August), and Trypanosoma brucei rhodesiense infection was confirmed by laboratory tests (on 14 August) including observation of parasites in blood films and by polymerase chain reaction. She was treated with pentamidine followed by suramin, and recovered 1 month later.

This is the first imported rhodesiense HAT case reported in China. This case alerts clinical and public health workers to be aware of HAT in travelers, and expatriates and migrants who have visited at-risk areas in Africa.