Volume 06 · Issue 06 · 2017

Diseases transmitted to humans by vectors account for 17%of all infectious diseases and remain significant public health problems. Through the years, great strides have been taken towards combatting vector-borne diseases （VBDs）, most notably through large scale and coordinated control programmes, which have contributed to the decline of the global mortality attributed to VBDs. However, with environmental changes, including climate change, the impact on VBDs is anticipated to be significant, in terms of VBD-related hazards, vulnerabilities and exposure. While there is growing awareness on the vulnerability of the African continent to VBDs in the context of climate change, there is still a paucity of research being undertaken in this area, and impeding the formulation of evidence-based health policy change.

One way in which the gap in knowledge and evidence can be filled is for donor institutions to support research in this area. The collaboration between the WHO Special Programme for Research and Training in Tropical Diseases （TDR） and the International Centre for Research and Development （IDRC） builds on more than 10 years of partnership in research capacity-building in the field of tropical diseases. From this partnership was born yet another research initiative on VBDs and the impact of climate change in the Sahel and sub-Saharan Africa. This paper lists the projects supported under this research initiative and provides a brief on some of the policy and good practice recommendations emerging from the ongoing implementation of the research projects.

Data generated from the research initiative are expected to be uptaken by stakeholders （including communities, policy makers, public health practitioners and other relevant partners） to contribute to a better understanding of the impacts of social, environmental and climate change on VBDs（i.e. the nature of the hazard, vulnerabilities, exposure）, and improve the ability of African countries to adapt to and reduce the effects of these changes in ways that benefit their most vulnerable populations.

Historically, the target in the schistosomiasis control has shifted from infection to morbidity, then back to infection, but now as a public health problem, before moving on to transmission control. Currently, all endemic countries are encouraged to increase control efforts and move towards elimination as required by the World Health Organization （WHO） roadmap for the global control of the neglected tropical diseases （NTDs） and the WHA65.21 resolution issued by the World Health Assembly. However, schistosomiasis prevalence is still alarmingly high and the global number of disability-adjusted life years （DALYs） due to this infection has in fact increased due to inclusion of some 'subtle' clinical symptoms not previously counted.

There is a need to restart and improve efforts to reach the elimination goal. To that end, the first conference of the Global Schistosomiasis Alliance （GSA） Research Working Group was held in mid-June 2016 in Shanghai, People's Republic of China. It reviewed current progress in schistosomiasis control and elimination, identified pressing operational research gaps that need to be addressed and discussed new tools and strategies required to make elimination a reality. The articles emanating from the lectures and discussions during this meeting, together with some additional invited papers, have been collected as a special issue of the 'Infectious Diseases of Poverty' entitled 'Schistosomiasis Research: Providing the Tools Needed for Elimination', consisting of 26papers in all. This paper refers to these papers and discusses critical questions arising at the conference related to elimination of schistosomiasis.

The currently most burning questions are the following: Can schistosomiasis be eliminated? Does it require better, more highly sensitive diagnostics? What is the role of preventive chemotherapy at the elimination stage? Is praziquantel sufficient or do we need new drugs? Contemplating these questions, it is felt that the heterogeneity of the endemic areas in the world requires WHO policies to be upgraded instituting new, differentiated guidelines.

It is difficult to quickly distinguish non-tuberculous mycobacterial （NTM） infection from tuberculosis（TB） infection in human immunodeficiency virus （HIV）-infected patients because of many similarities between these diseases. A simple and effective way to determine the differences using routine blood tests is necessary in developing countries.

A retrospective cohort study was conducted to recruit HIV-infected patients with either NTM infection or TB infection diagnosed for the first time according to mycobacterial culture and microscopic identification from May 2010 to March 2016. These data included the analysis of blood cells, liver function, renal function, C-reactive protein （CRP）, and erythrocyte sedimentation rate （ESR）, and were compared between the HIV/TB and HIV/NTM groups.

A total of 240 patients were enrolled. The number of HIV/TB and HIV/NTM patients was 113 and 127, respectively. There were no significant differences in the CD4 T-cell count, age, sex, percentage of patients initiating antiretroviral therapy （ART） before the explicit diagnosis of TB or NTM infection. NTM infection was more likely to be restricted in the pulmonary while TB infection also involves extra-pulmonary sites. Both the leukocyte count（5.60 × 10⁹/L） and the proportion of neutrophils in the leukocyte count （76.70%） in the HIV/TB group were significantly higher than those in the HIV/NTM group （4.40 × 10⁹/L [P=0.0014] and 69.30%[P <0.001]. The analysis of liver function markers indicated that the concentration of albumin but not ALT and AST was significantly lower in the HIV/TB group than in the HIV/NTM group (P <0.001）. The creatinine and urea levels were not significantly different between the two groups. The ESR （84.00 mm/h） and the concentration of CRP （59.60 mg/L） were significantly higher in the HIV/TB group than in the HIV/NTM group （52.00 mm/h and 19.60 mg/L, respectively） （P <0.001）. To distinguish TB infection from NTM infection, the best cut-off value was 69.5 mm/h for ESR, with a positive predictive value （PPV） of 0.740 and negative predictive value （NPV） of 0.721, and 48.8 mg/L for CRP, with a PPV of 0.676 and NPV of 0.697.（Continued on next page）

The dissemination character as well as stronger immune response characterized by higher inflammation markers (e.g. WBC, ESR, CRP) can help distinguish TB from NTM infection in HIV-infected patients who need empirical therapy or diagnostic therapy immediately in low-income areas.

Neglected tropical diseases (NTDs） prevail in conditions of poverty and contribute to the maintenance of social inequality. Out of the NTDs prioritized by the Brazilian Ministry of Health, four parasitic infections require mandatory notification: acute Chagas disease, leishmaniasis, malaria, and schistosomiasis. Data on the behaviour of these NTDs in the young population are currently limited. This study seeks to analyse the epidemiological aspects of these parasitic infections in children and adolescents in Brazil.

A retrospective exploratory ecological study was conducted. A spatial analysis of the cases reported between 2009 and 2013 in individuals aged between 0 and 19 years that were notified through the Health Notification Aggravation Information System （SINAN） was performed.

In total, 64,567 cases of cutaneous and visceral leishmaniasis, malaria, schistosomiasis, and acute Chagas disease were recorded in the SINAN database, representing a rate of 20.15 cases per 100,000 inhabitants. The average age of the cases was 12.2 years and 62.32%were male. Four hundred and three deaths related to these obligatorily reported parasites were recorded, indicating a case fatality rate of 0.62%. Visceral leishmaniasis and acute Chagas disease had the highest rates of lethality. A heterogeneous spatial distribution of the studied parasites was observed.

The number of cases and the lethality rate described in this study show that these diseases still represent a serious problem for public health in Brazil. This points to the need to encourage new research and the reformulation of social, economic, and public health policies aimed at ensuring better health and living conditions for all individuals, especially those among the populations considered vulnerable, as is the case of the young.

Malaria is a major public health problem in Myanmar. Migrant populations are at high risk of contracting malaria and its control is more difficult than for settled population. Studies on malaria and migration are rare in Myanmar. This study was undertaken with the main objective of identifying socioeconomic and behavioural determinants of malaria among the migrant workers involved in gold mining, rubber and oil palm plantations.

A cross-sectional analytic study was conducted using pretested interview-administered questionnaires among internal migrants （n=406） in the malaria endemic townships of Shwegyin, Bago Region, Thanbyuzayat, Mon State and Kawthaung, Taninthayi Region from August to November, 2015. Data were collected by well-trained Basic Health Staff members in study areas, and then analysed by SPSS version 16.0 using Chi-square tests with significant level at 0.05.

Majority of participants were male, Bahmar nationals, married and with primary basic education level and below. The mean duration of migratory work was 4.51 years. 43.1%of them gave definite previous history of malaria within last two years during migration. 92.9%（377/406） of them always used bed nets. Malaria determinants found were male gender （OR=1.84, 95% CI: 1.22-2.77; P=0.0040）, habit of going out at dawn （OR=236, 95% CI: 1.58-3.52;P <0.001）, usual sleeping indoors （OR=2.14, 95% CI: 1.04-4.42; P=0.036）, torn bed net or net with large hole（s）（OR=2.0,95% CI: 1.21-3.3; P=0.006）, habit of not always sleeping under a bed net at night （OR=2.02, 95% CI: 1.15-3. 52; P=0.014）, alcohol drinking （OR=2.71, 95% CI: 1.73-4.26; P <0.001） and failure to attend malaria health talk （OR=1. 78, 95% CI: 1.2-2.65; P=0.004）.

The present study highlighted that it is warranted to launch an effective health education programme for malaria, and to encourage the proper use of insecticide-treated bed nets, blankets and/or mufflers and mosquito repellents to reduce the occurrence of malaria among the migrants.

Prisons in Madagascar are at high risk of plague outbreak. Occurrence of plague epidemic in prisons can cause significant episode of urban plague through the movement of potentially infected humans, rodents and fleas. Rodent and flea controls are essential in plague prevention, by reducing human contact with plague reservoirs and vectors. Insecticide treatment is the key step available for the control of rat fleas which transmit the disease from infected rodents to human. The implementation of an adapted flea control strategy should rely on the insecticide susceptibility status of the targeted population. For the purpose of plague prevention campaign in prisons, we conducted insecticide resistance survey on Xenopsylla cheopis, the rat flea.

Fleas were collected on rats caught in six prisons of Madagascar. They were exposed to insecticide treated filter papers and mortality was recorded following World Health Organization protocol.

The fleas collected in the prisons had different resistance patterns, while a high level of resistance to insecticides tested was described in the Antanimora prison, located in the heart of Antananarivo, the capital of Madagascar.

This finding is alarming in the context of public health, knowing that the effectiveness of flea control could be jeopardized by insecticide resistance. In order to establish more accurate rat fleas control in prisons, the main recommendations are based on continuous monitoring insecticide susceptibility of flea, insecticide rotation, and the development of a new method for flea control.

Thymidine analogs, namely AZT （Zidovudine or Retrovir™） and d4T （Stavudine or Zerit™） are antiretroviral drugs still employed in over 75%of first line combination antiretroviral therapy （cART） in Kampala, Uganda despite aversion to prescribing these drugs for cART in high income countries due in part to adverse events. For this study, we explored how the continued use of these thymidine analogs in cART could impact emergence of drug resistance and impact on future treatment success in Uganda, a low-income country.

We examined the drug resistance genotypes by Sanger sequencing of 262 HIV-infected patients failing a first line combined antiretroviral treatment containing either AZT or d4T, which represents approximately 5%of the patients at the Joint Clinical Research Center receiving a AZT or d4T containing treatment. Next generation sequencing （DEEPGEN™HIV） and multiplex oligonucleotide ligation assays （AfriPOLA） were then performed on a subset of patient samples to detect low frequency drug resistant mutations. CD4 cell counts, viral RNA loads, and treatment changes were analyzed in a cohort of treatment success and failures.

Over 80%of patients failing first line AZT/d4T-containing cART had predicted drug resistance to 3TC （Lamivudine）and non-nucleoside RT inhibitors （NNRTIs） in the treatment regimen but only 45%had resistance AZT/d4T associated resistance mutations （TAMs）. TAMs were however detected at low frequency within the patients HIV quasispecies （1-20%） in 21 of 34 individuals who were failing first-line AZT-containing cART and lacked TAMs by Sanger. Due to lack of TAMs by Sanger, AZT was typically maintained in second-line therapies and these patients had a low frequency of subsequent virologic success.

Our findings suggest that continued use of AZT and d4T in first-line treatment in low-to-middle income countries may lead to misdiagnosis of HIV-1 drug resistance and possibly enhance a succession of second- and third-line treatment failures.

Neglected tropical diseases （NTDs） are an important cause of death and disability in Africa. This study estimates the monetary value of human lives lost due to NTDs in the continent in 2015.

The lost output or human capital approach was used to evaluate the years of life lost due to premature deaths from NTDs among 10 high/upper-middle-income （Group 1）, 17 middle-income （Group 2） and 27 low-income（Group 3） countries in Africa. The future losses were discounted to their present values at a 3%discount rate. The model was re-analysed using 5%and 10%discount rates to assess the impact on the estimated total value of human lives lost. Results: The estimated value of 67 860 human lives lost in 2015 due to NTDs was Int$ 5 112472 607. Out of that, 14.6%was borne by Group 1, 57.7%by Group 2 and 27.7%by Group 3 countries. The mean value of human life lost per NTD death was Int$ 231 278, Int$ 109 771 and Int$ 37489 for Group 1, Group 2 and Group 3 countries, respectively. The estimated value of human lives lost in 2015 due to NTDs was equivalent to 0.1% of the cumulative gross domestic product of the 53 continental African countries.

Even though NTDs are not a major cause of death, they impact negatively on the productivity of those affected throughout their life-course. Thus, the case for investing in NTDs control should also be influenced by the value of NTD morbidity, availability of effective donated medicines, human rights arguments, and need to achieve the NTD-related target 3.3 of the United Nations Sustainable Development Goal 3 （on health） by 2030.

The 2014-2016 Ebola crisis in West Africa had approximately eight times as many reported deaths as the sum of all previous Ebola outbreaks. The outbreak magnitude and occurrence of multiple Ebola cases in at least seven countries beyond Liberia, Sierra Leone, and Guinea, hinted at the possibility of broad-scale transmission of Ebola.

Using a modeling tool developed by the US Centers for Disease Control and Prevention during the Ebola outbreak, we estimated the number of Ebola cases that might have occurred had the disease spread beyond the three countries in West Africa to cities in other countries at high risk for disease transmission （based on late 2014 air travel patterns）. We estimated Ebola cases in three scenarios: a delayed response, a Liberia-like response, and a fast response scenario. Based on our estimates of the number of Ebola cases that could have occurred had Ebola spread to other countries beyond the West African foci, we emphasize the need for improved levels of preparedness and response to public health threats, which is the goal of the Global Health Security Agenda. Our estimates suggest that Ebola could have potentially spread widely beyond the West Africa foci, had local and international health workers and organizations not committed to a major response effort. Our results underscore the importance of rapid detection and initiation of an effective, organized response, and the challenges faced by countries with limited public health systems. Actionable lessons for strengthening local public health systems in countries at high risk of disease transmission include increasing health personnel, bolstering primary and critical healthcare facilities, developing public health infrastructure （e.g. laboratory capacity）, and improving disease surveillance. With stronger local public health systems infectious disease outbreaks would still occur, but their rapid escalation would be considerably less likely, minimizing the impact of public health threats such as Ebola.

The Ebola outbreak could have potentially spread to other countries, where limited public health surveillance and response capabilities may have resulted in additional foci. Health security requires robust local health systems that can rapidly detect and effectively respond to an infectious disease outbreak.

Echinococcosis is a neglected zoonotic disease, causing great morbidity and mortality due to the wide distribution of its endemic areas. China holds a high percentage in the global burden of both cystic and alveolar echinococcosis. A national survey conducted between 2012 and 2016 showed that an estimated 50 million people are at risk of contracting the disease in western China, of whom about 0.17 million are cases with echinococcosis. Despite this, research and development on echinococcosis in China is greatly inadequate compared to that in other countries. In this paper, we argue that there is a need for more research and work to be conducted in China on echinococcosis, including researching techniques in regards to diagnosis, treatment, and vaccination, and developing products through technical transformation and piloting strategies to control and even elimination. However, great opportunities exist for China to strengthen the research and development on this disease through initiatives such as Health China 2030, the Belt and Road Initiative, the China-Africa cooperation, as well as through further cooperation between China and the World Health Organization. All of these can bring us closer to controlling echinococcosis in China as well as in other countries. One element of crucial importance will be the training and development of professionals, which can be strengthened through international cooperation.

In the underdeveloped multi-ethnic regions of China, high tuberculosis （TB） burden and regional inequity in access to healthcare service increase the challenge of achieving the End TB goals. Among all the provinces, the highest TB burden is reported in Xinjiang, where ethnic minorities and older people have suffered most. However, current case-finding strategy is inadequate given the complex social determinants and suboptimal case detection rates. Thus, we developed an integrated TB control program to improve case detection and conducted a pilot in Xinjiang from 2014 to 2015. In this case study, we summarized the activities and key findings. We also shared the experiences and challenges of implementing interventions and provided recommendations to inform the TB control program in the future.

The pilot interventions were implemented in one selected town in Yining based on local TB control programs. By applying tailor-made educational materials, outreach TB educational activities were conducted in diverse ways. In 22 Masjids, the trained imams promoted TB education to the Muslims, covering 20,440 person-times in 88 delivered preaching sessions. In seven schools, 1944 students were educated by the teachers and contributed to educating 6929 family members. In the village communities, 13,073 residents participated in household education and screening. Among them, 12,292 people aged under 65 years were investigated for suspicious pulmonary TB symptoms, where six TB patients were diagnosed out of 89 TB suspects; 781 older people were mobilized for screening directly by chest X-ray, where 10 patients were diagnosed out of 692 participants. Supportive healthcare system, multi-sectoral cooperation and multi-channel financing mechanism were the successful experiences of implementation. The interventions were proved to be more effective than the previous performance: the number of TB suspects consulting doctors and patients detected increased by 50%and 26%, respectively. The potential challenges, implications and recommendations should been taken into account for further program improvement.

In underdeveloped multi-ethnic regions with high TB burden, improving case detection is necessary and the interventions can be feasible and effective within a supportive system. More intensive educational and training approaches, a high index of TB suspicion and prioritization of older people in screening are recommended. To sustain and scale up the program, the impacts, cost-effectiveness, feasibility and acceptability of interventions warrant further research and evaluation in each specific context.

本文发表后[1我们注意到陈俊和鲁洪洲的从属关系显示不正确。