2019年 · 第08卷第04期

Onchocerciasis (river blindness), caused by the filarial worm species Onchocerca volvulus, is a serious vector-borne neglected tropical disease (NTD) of public health and socioeconomic concern. It is transmitted through the bite of black flies of the genus Simulium, and manifested in dermal and ocular lesions. Ninety-nine percent of the total global risk and burden of onchocerciasis is in Africa. This scoping review examines the key challenges related to the elimination of onchocerciasis by 2020-2025 in Africa, and proposes recommendations to overcome the challenges and accelerate disease elimination. To find relevant articles published in peer-reviewed journals, a search of PubMed and Google Scholar databases was carried out.

Rigorous regional interventions carried out to control and eliminate onchocerciasis in the past four decades in Africa have been effective in bringing the disease burden under control; it is currently not a public health problem in most endemic areas. Notably, transmission of the parasite is interrupted in some hyperendemic localities. Recently, there has been a policy shift from control to complete disease elimination by 2020 in selected countries and by 2025 in the majority of endemic African countries. The WHO has published guidelines for stopping mass drug administration (MDA) and verifying the interruption of transmission and elimination of human onchocerciasis. Therefore, countries have revised their plans, established a goal of disease elimination in line with an evidence based decision to stop MDA and verify elimination, and incorporated it into their NTDs national master plans. Nevertheless, challenges remain pertaining to the elimination of onchocerciasis in Africa. The challenge we review in this paper are: incomplete elimination mapping of all transmission zones, co-endemicity of onchocerciasis and loiasis, possible emergence of ivermectin resistance, uncoordinated cross-border elimination efforts, conflict and civil unrest, suboptimal program implementation, and technical and financial challenges. This paper also proposes recommendations to overcome the challenges and accelerate disease elimination. These are: a need for complete disease elimination mapping, a need for collaborative elimination activities between national programs, a need for a different drug distribution approach in conflict-affected areas, a need for routine monitoring and evaluation of MDA programs, a need for implementing alternative treatment strategies (ATSs) in areas with elimination anticipated beyond 2025, and a need for strong partnerships and continued funding.

National programs need to regularly monitor and evaluate the performance and progress of their interventions, while envisaging the complete elimination of onchocerciasis from their territory. Factors hindering the targeted goal of interruption of parasite transmission need to be identified and remedial actions should be taken. If possible and appropriate, ATSs need to be implemented to accelerate disease elimination by 2025.

The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in response to the call proposed at the 50th World Health Assembly. The goal of the GPELF is to ensure that all the countries where the disease is endemic would have been transmission-free or would have entered post-intervention mass drug administration (MDA) surveillance by 2020. However, several countries are still not on track to discontinue MDA as planned. Thus, issues remain regarding the achievement of stated goals and how to effectively monitor the disease in the post-control and post-elimination phases.

China was once a lymphatic filariasis (LF) endemic country with heavy disease burden. There were three milestones in the LF control phase of China, including: the proposal that the major focus of the control strategy should be on infectious sources; the three regimens of diethylcarbamazine (DEC) administration according to LF endemic extent; and the establishment of the threshold for LF transmission interruption. It has been ten years since China entered the post-elimination stage (declaration of LF elimination in China was in 2007). Two schemes and a diagnostic criterion were issued to guide all levels of disease control and prevention workers that conduct LF surveillance, as well as those caring for chronic filariasis patients. Regular training courses are held to maintain LF control skills in grass-root institutions. The Notifiable Diseases Reporting System, which included LF in 2004, plays an important role in LF post-elimination surveillance. Until now, no resurgence of LF cases has been detected, except for LF residue foci being found in Fuchuan County of the Guangxi Zhuang Autonomous Region. To confirm that transmission is no longer achievable after a decade since the declaration of LF elimination in China, it is expected within the next two years a transmission assessment survey, conducted in previous LF-endemic areas.

DEC-fortified salt can help accelerate the progress of GPELF before the sprite phase. Sophisticated diagnostic criteria, systematic surveillance regimes, the Direct Network Report system, and regular trainings can effectively prevent the recrudescence of LF during surveillance phases.

Baseline mapping of soil-transmitted helminth (STH) infections among school age children (SAC) in 2008-2009 found high or moderate prevalence in 13 of the 14 districts in Sierra Leone. Following these surveys, mass drug administration (MDA) of mebendazole/albendazole was conducted biannually at national level targeting pre-school children (PSC) aged 12-59 months and intermittently at sub-national level targeting SAC. In addition, MDA with ivermectin and albendazole for eliminating lymphatic filariasis (LF) has been conducted nationwide since 2010 targeting individuals over 5 years of age. Each MDA achieved high coverage, except in 2014 when all but one round of MDA for PSC was cancelled due to the Ebola emergency. The objective of the current study was to determine the prevalence and intensity of STH infections among SAC after a decade of these deworming campaigns.

Seventy-three schools in 14 districts were purposefully selected, including 39 schools from the baseline surveys, with approximately two sites from each of low, moderate and high prevalence categories at baseline per district. Fresh stool samples were collected from 3632 children aged 9-14 years (male 51%, female 49%) and examined using the Kato Katz technique.

The prevalence of STH infections in Sierra Leone decreased in 2016 compared to 2008: Ascaris lumbricoides 4.4% (95% confidence interval [CI]: 3.7-5.1%) versus 6.6% (95% CI: 0-25%), Trichuris trichiura 0.7% (95% CI: 0.5-1.1%) versus 1.8% (95% CI: 0-30.2%), hookworm 14.9% (95% CI: 13.8-16.1) versus 38.5% (95% CI: 5.4-95.1%), and any STH 18.3% (95% CI:17.0-19.5%) versus 48.3% (CI: 5.4-96.3%), respectively. In 2016, no district had high hookworm prevalence and four districts had moderate prevalence, compared with eight and four districts respectively in 2008. In 2016, the arithmetic mean hookworm egg count in all children examined was light: 45.5 eggs per gram (EPG) of faeces, (95% CI:\35.96-55.07 EPG); three (0.08%) children had heavy infections and nine (0.25%) children had moderate infections.

Sierra Leone has made considerable progress toward controlling STH as a public health problem among SAC. As LF MDA phases out (between 2017 and 2021), transition of deworming to other platforms and water and sanitation strategies need to be strengthened to maintain STH control and ultimately interrupt transmission.

The wetlands used for some agricultural activities constitute productive breeding sites for many mosquito species. Thus, the agricultural use of insecticide targeting other pests may select for insecticide resistance in malaria mosquitoes. The purpose of this study is to clarify some knowledge gaps on the role of agrochemicals in the development of insecticide resistance in malaria vectors is of utmost importance for vector control.

Using the CDC bottle test and the log-probit analysis, we investigated for the first time the resistance levels of Anopheles coluzzii mosquitoes to neonicotinoids, insecticides used exclusively for crop protection in Côte d'Ivoire. The study was conducted in two agricultural regions (Tiassale and Gagnoa) and one non-agricultural region (Vitre) between June and August 2017 using clothianidin, acetamiprid and imidacloprid.

Mosquito populations from Tiassale and Gagnoa (agricultural settings) were determined to be resistant to acetamiprid with mortality rates being <85% at 24 h post-exposure. In Vitre (non-agricultural area) however, the mosquito population was susceptible to acetamiprid. In all three localities, mosquito populations were resistant to imidacloprid (mortality rates were 60% in Vitre, 37% in Tiassale, and 13% in Gagnoa) and completely susceptible to clothianidin (100% mortality). An. coluzzii represented 100% of mosquito collected in Gagnoa, 86% in Tiassale and 96% in Vitre.

This study provides strong evidence that agricultural use of insecticides can cause insecticide resistance in malaria vector populations. Insecticide resistance driven by agrochemical usage should be considered when vector control strategies are developed.

Echinococcosis caused by Echinococcus is one of the most major infectious diseases in north-west highland of China. E. granulosus sensu strict, E. multilocularis, and E. canadensis are known to be the only three species related to human health transmitting in the areas. To achieve targeted treatment and control of echinococcosis, the accurate identification and discrimination of the species are important. However, currently the available diagnostic approaches do not present ideal results either in accuracy or efficiency.

In the study, a set of primers were designed to aim at the three human-pathogenic Echinococcus species in China. The one-step multiplex PCR assay was developed and evaluated for the specificity and sensitivity. A total of 73parasitic lesions and 41 fecal materials obtained from human and various animals collected in the clinic and the field were tested to assess the applicability of this method.

The multiplex PCR effectively detected the individual DNA from the targeted species and their random mixtures generating with distinguishable expected size of products. The detection limit of the assay for each of the three species was 5 pg/μl when they were tested separately. When DNA mixtures of the targeted species containing the same concentration were used as templates, the lowest amount of DNA which can be detected was 50 pg/μl, 10 pg/μl and 5 pg/μl for E. granulosus s. s., E. multilocularis, and E. canadensis respectively. No cross-reactivity was observed when DNA from eight genetically close species was used as control templates. The multiplex PCR identifications of all samples were in line with the original sequencing results except for those infected with E. shiquicus, which showed negative signals in the developed assay. Of all the tested stool materials, 16 were previously found positive for Echinococcus by visual and microscopic examination. Among these 16 samples, 13 were confirmed by the multiplex PCR, and the other three tested negative. Additionally, the multiplex PCR identified another 14 positive feces from the remained 25 stool samples which absence of worms.

The developed multiplex PCR shows advantages in fast diagnosis and large-scale epidemiological investigation, which proven to be a promising tool utilized in clinic and surveillance system.

Tuberculosis (TB) patient management (TPM) is crucial to improve patient compliance to treatment. The coverage of TPM delivered by TB dispensaries or Centers for Disease Control and Prevention (CDC) was not high under the previous CDC model of TB control in China. In the integrated TB control model in China, TB patient management (TPM) was mainly delivered by lay health workers (LHWs) in primary health care (PHC) sectors. This study aims to investigate TPM delivery in resource-limited western China and to identify factors affecting TPM delivery by LHWs under the integrated TB control model.

A stratified random sampling was used to select study sites. Pulmonary TB (PTB) patients ≥15 years old from selected counties/districts in Guizhou Province were surveyed from August 2015 to May 2016. Structured questionnaires were used to collect data. A χ² test and logistic regression were used to identify factors associated with self-administered treatment (non-TPM).

In total, 638 PTB patients were included in the final analysis. Close to 30% of patients were ethnic minorities. More than 30% of patients were from counties with high TB burden, and 24.9% of patients had poor compliance to treatment. Only 37.1% of patients received TPM delivered by LHWs under the integrated TB control model throughout the treatment period. The main reasons for unwillingness to manage reported by patients included social stigma and no perceived need. Being ethnic minorities (OR=3.35) was a main factor associated with lower likelihood of receiving TPM, while living in areas with middle or high TB burden may increase the likelihood of receiving TPM (OR=0.17 and 0.25, respectively). Among current management approaches, more than 85% of patients chose phone reminder as their preferred TPM by LHWs.

TPM under the integrated model in West China is still low and need further improvement, and the impeding factors of TPM need to be addressed. Strengthening patient-centered and community-based TPM and developing more feasible approaches of TPM delivery should be explored in future research in this region.

Over 90% of Human Immunodeficiency Virus (HIV) infected individuals will be on treatment by 2020under UNAIDS 90-90-90 global targets. Under World Health Organisation (WHO) "Treat All" approach, this number will be approximately 36.4 million people with over 98% in low-income countries (LICs).

Pretreatment drug resistance (PDR) largely driven by frequently use of non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz and nevirapine, has been increasing with roll-out of combined antiretroviral therapy (cART) with 29% annual increase in some LICs countries. PDR has exceeded 10% in most LICs which warrants change of first line regimen to more robust classes under WHO recommendations. If no change in regimens is enforced in LICs, it's estimated that over 16% of total deaths, 9% of new infections, and 8% of total cART costs will be contributed by HIV drug resistance by 2030. Less than optimal adherence, and adverse side effects associated with currently available drug regimens, all pose a great threat to achievement of 90% viral suppression and elimination of AIDS as a public health threat by 2030. This calls for urgent introduction of policies that advocate for voluntary and compulsory drug licensing of new more potent drugs which should also emphasize universal access of these drugs to all individuals worldwide.

The achievement of United Nations Programme on HIV and AIDS 2020 and 2030 targets in LICs depends on access to active cART with higher genetic barrier to drug resistance, better safety, and tolerability profiles. It's also imperative to strengthen quality service delivery in terms of retention of patients to treatment, support for adherence to cART, patient follow up and adequate drug stocks to help achieve a free AIDS generation.

Gonorrhea and chlamydia testing rates are poor among Chinese men who have sex with men (MSM). A quasi-experimental study suggested that a pay-it-forward strategy increased dual gonorrhea/chlamydia testing among MSM. Pay-it-forward offers an individual a gift (e.g., a free test) and then asks the same person if they would like to give a gift to another person. This article reports the protocol of a randomized controlled trial to evaluate dual gonorrhea/chlamydia test uptake and other outcomes among MSM in three arms - a pay-it-forward arm, a pay-what-you-want arm, and a standard of care arm.

Three hundred MSM will be recruited at three HIV testing sites in Guangzhou and Beijing. Testing sites include two hospital-based MSM sexually transmitted diseases clinics and one MSM community-based organization. Eligible participants will be born biologically male, aged 16 years or older, reporting previous anal sex with another man, having never participated in the pay-it-forward program, without previous gonorrhea and chlamydia testing in the past 12 months, and residing in China. Following a cluster randomized design, every cluster of ten participants will be randomly allocated into one of three arms: (1) a pay-it-forward arm in which men are offered free gonorrhea and chlamydia testing and then asked whether they would like to donate ("pay it forward") toward testing for future testers; (2) a pay-what-you-want arm in which men are offered free testing and told to decide how much to pay after receiving the test; (3) a standard of care arm in which men can pay the full price for dual gonorrhoea and chlamydia testing. The primary outcome is dual gonorrhoea/chlamydia testing as verified by administrative records. Secondary outcomes include incremental cost per test, incremental cost per diagnosis, community connectedness, and social cohesion. Primary outcome will be calculated for each arm using intention-to-treat and compared using one-sided 95% confidence intervals with a margin of 20% increase defined as superiority.

This study will examine the pay-it-forward strategy in comparison to the standard of care in improving test uptake for gonorrhea and chlamydia. We will leverage the cluster randomized controlled trial to provide scientific evidence on the potential effect of pay-it-forward. Findings from this study will shed light on novel intervention methods for increasing preventive health service utilization and innovate ways to finance it among communities.

ClinicalTrials.gov, NCT03741725. Registered on 12 November 2018.