The response to COVID-19 in Timor-Leste: lessons learnt.

The response to the COVID-19 pandemic in Timor-Leste offers lessons that may be useful for incorporating into future responses to infectious disease outbreaks in similar resource-limited settings. In this paper, we identify nine key areas for learning from Timor-Leste's experience of the COVID-19 pandemic: (1) the importance of prior preparation for health emergencies, (2) the establishment of effective leadership and governance structures, (3) the protective impact of early border restrictions, (4) the rapid expansion of diagnostic laboratory capacity, (5) the impact of effective health communications in supporting the vaccine roll-out, (6) the opportunity to build capacity for clinical care, (7) the use of public health interventions that were found to have limited public health impact, (8) the broader effects of the pandemic and the public health response and (9) translation of lessons from COVID-19 to other public health priorities.

Novel compact high-speed passive gamma-ray assay equipment for uranium enrichment measurement of fuel rods.

Uranium enrichment measurement is an essential quality inspection for fuel rods before delivery to users. Generally, compared with active neutron assay (ANA) equipment, passive gamma-ray assay (PGA) equipment is more economical and safer. However, the current PGA equipment based on photomultipliers is too slow (1 m/min) to meet the growing needs in China. Recently, we have developed a set of compact high-speed PGA equipment including four detection modules (128 units in total), a 128-channel data acquisition system (DAS), a power supply, special software, and an automatic loading and unloading mechanism. The detection unit is based on silicon photomultipliers in virtue of its compact size and good performance. The DAS processes signals of all units in parallel into a sequence of data packets carrying the energy information and the corresponding unit ID. The software integrates the data packets into a fluctuating count curve in a time-delay superposition method and identifies possible abnormal pellets. After calibrations, our equipment can locate abnormal pellets accurately at a speed of 6 m/min. In addition, it can directly measure the enrichment of fresh pellets not in secular equilibrium without waiting for two months. So far, the equipment has been successfully run for one year on the assembly line of China North Nuclear Fuel Co. and shows good potential to replace the traditional ANA equipment.

Evolution of the Gut Microbiome in Early Childhood: A Cross-Sectional Study of Chinese Children.

Temporal development of the human gut microbiome from infancy to childhood is driven by a variety of factors. We surveyed the fecal microbiome of 729 Chinese children aged 0-36 months, aiming to identify the age-specific patterns of microbiota succession, and evaluate the impact of birth mode, gender, geographical location, and gastrointestinal tract symptoms on the shaping of the gut microbiome. We demonstrated that phylogenetic diversity of the gut microbiome increased gradually over time, which was accompanied by an increase in Bacteroidetes and a reduction in Proteobacteria species. Analysis of community-wide phenotypes revealed a succession from aerobic bacteria and anaerobic bacteria to facultative anaerobes, and from Gram-negative to Gram-positive species during gut microbiota development in early childhood. The metabolic functions of the gut microbiome shifted tremendously alongside early physiological development, including an increase in alanine, aspartate, and glutamate metabolism, and a reduction in glutathione, fatty acid, and tyrosine metabolism. During the first year of life, the Bacteroidetes phylum was less abundant in children born by casarean section compared with those delivered vaginally. The Enterococcaceae family, a group of facultative anaerobic microorganisms with pathogenic potential, was predominant in preterm infants. No measurable effect of maternal antibiotic exposure on gut microbiota development was found in the first 3 years of life. The relative abundances of Coriobacteriaceae and Streptococcaceae families, and Megasphaera genus were found to be higher in girls than in boys. Among the three first-tier Chinese cities, children born and fed in Beijing had a higher abundance of Enterococcaceae and Lachnospiraceae families, and Shenzhen children had a higher abundance of Fusobacteriaceae. The families Alcaligenaceae, Bacteroidaceae, and Porphyromonadaceae were more abundant in children with constipation, whereas the relative abundance of the Clostridium genus was higher in those with diarrhea.

Gut Microbiota Dysbiosis Is Associated with Altered Bile Acid Metabolism in Infantile Cholestasis.

The co-occurrence of gut microbiota dysbiosis and bile acid (BA) metabolism alteration has been reported in several human liver diseases. However, the gut microbiota dysbiosis in infantile cholestatic jaundice (CJ) and the linkage between gut bacterial changes and alterations of BA metabolism have not been determined. To address this question, we performed 16S rRNA gene sequencing to determine the alterations in the gut microbiota of infants with CJ, and assessed their association with the fecal levels of primary and secondary BAs. Our data reveal that CJ infants show marked declines in the fecal levels of primary BAs and most secondary BAs. A decreased ratio of cholic acid (CA)/chenodeoxycholic acid (CDCA) in infants with CJ indicated a shift in BA synthesis from the primary pathway to the alternative BA synthesis pathway. The bacterial taxa enriched in infants with CJ corresponded to the genera Clostridium, Gemella, Streptococcus, and Veillonella and the family Enterobacteriaceae and were negatively correlated with the fecal BA level and the CDCA/CA ratio but positively correlated with the serological indexes of impaired liver function. An increased ratio of deoxycholic acid (DCA)/CA was observed in a proportion of infants with CJ. The bacteria depleted in infants with CJ, including Bifidobacterium and Faecalibacterium prausnitzii, were positively and negatively correlated with the fecal levels of BAs and the serological markers of impaired liver function, respectively. In conclusion, the reduced concentration of BAs in the gut of infants with CJ is correlated with gut microbiota dysbiosis. The altered gut microbiota of infants with CJ likely upregulates the conversion from primary to secondary BAs.IMPORTANCE Liver health, fecal bile acid (BA) concentrations, and gut microbiota composition are closely connected. BAs and the microbiome influence each other in the gut, where bacteria modify the BA profile, while intestinal BAs regulate the growth of commensal bacteria, maintain the barrier integrity, and modulate the immune system. Previous studies have found that the co-occurrence of gut microbiota dysbiosis and BA metabolism alteration is present in many human liver diseases. Our study is the first to assess the gut microbiota composition in infantile cholestatic jaundice (CJ) and elucidate the linkage between gut bacterial changes and alterations of BA metabolism. We observed reduced levels of primary BAs and most secondary BAs in infants with CJ. The reduced concentration of fecal BAs in infantile CJ was associated with the overgrowth of gut bacteria with a pathogenic potential and the depletion of those with a potential benefit. The altered gut microbiota of infants with CJ likely upregulates the conversion from primary to secondary BAs. Our study provides a new perspective on potential targets for gut microbiota intervention directed at the management of infantile CJ.

Helicobacter pylori infection alters gastric and tongue coating microbial communities.

OBJECTIVE: Infection with Helicobacter pylori (H pylori), especially cytotoxin-associated gene A-positive (CagA+) strains, has been associated with various gastrointestinal and extragastric diseases. The aim of this study was to characterize H pylori-induced alterations in the gastric and tongue coating microbiota and evaluate their potential impacts on human health. DESIGN: The gastric mucosa and tongue coating specimens were collected from 80 patients with chronic gastritis, and microbiota profiles were generated by 16S rRNA gene sequencing. Samples were grouped as H pylori negative (n = 32), CagA-negative H pylori infection (n = 13), and CagA-positive H pylori infection (n=35). The comparison of bacterial relative abundance was made using a generalized linear model. Functional profiling of microbial communities was predicted with PICRUSt and BugBase. Microbial correlation networks were produced by utilizing SparCC method. RESULTS: Significant alterations of the gastric microbiota were found in the H pylori+/CagA+ samples, represented by a decrease in bacterial diversity, a reduced abundance of Roseburia, and increased abundances of Helicobacter and Haemophilus genera. At the community level, functions involved in biofilm forming, mobile element content, and facultative anaerobiosis were significantly decreased in gastric microbiome of the H pylori+ subjects. The presence of CagA gene was linked to an increased proportion of Gram-negative bacteria in the stomach, thereby contributing to an upregulation of lipopolysaccharide (LPS) biosynthesis. The number of bacterial interactions was greatly reduced in networks of both tongue coating and gastric microbiota of the H pylori+/CagA+ subject, and the cooperative bacterial interactions dominated the tongue coating microbiome. CONCLUSIONS: Infection with H pylori strains possessing CagA may increase the risk of various diseases, by upregulating LPS biosynthesis in the stomach and weakening the defense of oral microbiota against microorganisms with pathogenic potential.

Clinical Efficacy and Microbiome Changes Following Fecal Microbiota Transplantation in Children With Recurrent Clostridium Difficile Infection.

Fecal microbiota transplantation (FMT) has been shown as an effective treatment for recurrent clostridium difficile infection (RCDI) in adults. In this study, we aim to evaluate the clinical efficacy of FMT in treating children with RCDI, and explore fecal microbiota changes during FMT treatment. A total of 11 RCDI subjects with a median age of 3.5 years were enrolled in this single-center prospective pilot study. All patients were cured (11/11, 100%) by FMT either through upper gastrointestinal tract route with a nasointestinal tube (13/16, 81.2%) or lower gastrointestinal tract route with a rectal tube (3/16, 18.8%). The cure rate of single FMT was 63.6% (7/11), and 4 (4/11, 36.4%) cases were performed with 2 or 3 times of FMT. Mild adverse events were reported in 4 children (4/11, 36.4%), including transient diarrhea, mild abdominal pain, transient fever and vomit. Gut microbiota composition analysis of 59 fecal samples collected from 34 participants (9 RCDI children, 9 donors and 16 health controls) showed that the alpha diversity was lower in pediatric RCDI patients before FMT than the healthy controls and donors, and fecal microbial community of pre-FMT samples (beta diversity) was apart from that of healthy controls and donors. No significant differences in alpha diversity, beta diversity or phylogenetic distance were detected between donors and healthy controls. Both the richness and diversity of gut microbiota were improved in the pediatric RCDI patients after FMT, and the bacteria community was shifted closer to the donor and healthy control group. Furthermore, FMT re-directed gut microbiome functions of pediatric RCDI toward a health state. Our results indicate that it is safe and tolerant to use FMT in treating pediatric RCDI. FMT shifted the gut microbiome composition and function in children with RCDI toward a healthy state.

HIV/AIDS in the South-East Asia region: progress and challenges.

The South-East Asia region, with 11 member states, has an estimated 3.5 million people living with HIV (PLHIV). More than 99% of PLHIV live in five countries where HIV prevalence among the population aged 15-49 remains low but is between 2% and 29% among key populations. Since 2010, the region has made progress to combat the epidemic. Mature condom programmes exist in most countries but opioid substitution therapy, and needle and syringe exchange programmes need to be scaled up. HIV testing is recommended nationwide in four countries and is prioritised in high prevalence areas or for key populations in the rest. In 2015, PLHIV aware of their HIV status ranged from 26% to 89%. Antiretroviral therapy (ART) is recommended for all PLHIV in Thailand and Maldives while six countries recommend ART at CD4 cell counts <500 cells/mm3. In 2015, 1.4 million (39%) PLHIV were receiving ART compared to 670,000 (20%) in 2010. Coverage of HIV testing and treatment among HIV-positive pregnant women has also improved but remains low in all countries except Thailand, which has eliminated mother-to-child transmission of HIV and syphilis. Between 2010 and 2015, AIDS-related deaths and new HIV infections have shown a declining trend in all the high-burden countries except Indonesia. But the region is far from achieving the 90-90-90 target by 2020 and the end of AIDS by 2030. The future HIV response requires that governments work in close collaboration with communities, address stigma and discrimination, and efficiently invest domestic resources in evidence-based HIV testing and treatment interventions for populations in locations that need them most.

Feasibility of implementing an integrated tool for improvement of treatment quality and early-warning indicators for HIV drug resistance: a pilot study of centres in India.

With the rapid scale-up in use of antiretroviral therapy (ART), monitoring the quality of care and factors that may lead to emergence of HIV drug resistance (HIVDR) is an important focus point for programme managers. The National AIDS Control Organisation of India embarked on strengthening the ART programme for continuous quality improvement (CQI), using defined quality-of-care indicators (QCIs), including World Health Organization (WHO) early-warning indicators (EWIs) for HIVDR. In this feasibility study, done during July 2014, an integrated QCI and EWI tool developed by WHO India was pilot tested across 18 purposively selected ART centres. At seven ART centres, the EWI 1 target of >90% on-time pill pick-up was achieved for adult patients, while among the paediatric age group (<15 years old) it was not achieved by any centre. EWI 2 (retention of patients in ART care at 12 months after initiation) showed that two centres had retention of both adult and paediatric patients of >85% at 12 months of ART, while 11 centres had retention between 75% and 85%. EWI 3 (pharmacy stock-out) for adult and paediatric patients showed that 11 ART centres reported a minimum of one stock-out for the first-line ART drugs in the reporting period, while EWI 4 targets (pharmacy dispensing practices) were achieved by all the centres, for both adults and children. Average retention in care at 6, 12 and 24 months after ART initiation was 82%, 77% and 71%, respectively. This feasibility study showed that EWI analyses were much simpler to conduct if information was sought only for patients receiving ART, for whom the quality of record-keeping is better and more consistent. The activity has highlighted the need for improved quality of record-keeping at the facilities and implementation of specific interventions to ensure better patient follow-up. After modifications, use of the tool will be phased in across all the ART centres in India.

Estimating the size of key populations at higher risk of HIV infection: a summary of experiences and lessons presented during a technical meeting on size estimation among key populations in Asian countries.

PROBLEM: Size estimates of key populations at higher risk of HIV exposure are recognized as critical for understanding the trajectory of the HIV epidemic and planning and monitoring an effective response, especially for countries with concentrated and low epidemics such as those in Asia. CONTEXT: To help countries estimate population sizes of key populations, global guidelines were updated in 2011 to reflect new technical developments and recent field experiences in applying these methods. ACTION: In September 2013, a meeting of programme managers and experts experienced with population size estimates (PSE) for key populations was held for 13 Asian countries. This article summarizes the key results presented, shares practical lessons learnt and reviews the methodological approaches from implementing PSE in 13 countries. LESSONS LEARNT: It is important to build capacity to collect, analyse and use PSE data; establish a technical review group; and implement a transparent, well documented process. Countries should adapt global PSE guidelines and maintain operational definitions that are more relevant and useable for country programmes. Development of methods for non-venue-based key populations requires more investment and collaborative efforts between countries and among partners.

Challenges and potential barriers to the uptake of antiretroviral-based prevention in Asia and the Pacific region.

Evidence has emerged over the past few years on the effectiveness of antiretroviral-based prevention technologies to prevent (i) HIV transmission while decreasing morbidity and mortality in HIV-infected persons, and (ii) HIV acquisition in HIV-uninfected individuals through pre-exposure prophylaxis (PrEP). Only few of the planned studies on treatment as prevention (TasP) are conducted in Asia. TasP might be more feasible and effective in concentrated rather than in generalised epidemics, as resources for HIV testing and antiretroviral treatment could focus on confined and much smaller populations than in the generalised epidemics observed in sub-Saharan Africa. Several countries such as Cambodia, China, Thailand and Vietnam, are now paving the way to success. Similar challenges arise for both TasP and PrEP. However, the operational issues for PrEP are amplified by the need for frequent retesting and ensuring adherence. This paper describes challenges for the implementation of antiretroviral-based prevention and makes the case that TasP and PrEP implementation research in Asia is much needed to provide insights into the feasibility of these interventions in populations where firm evidence of 'real world' effectiveness is still lacking.

Estimating the size of key populations at higher risk of HIV infection: a summary of experiences and lessons presented during a technical meeting on size estimation among key populations in Asian countries

Problem:Size estimates of key populations at higher risk of HIV exposure are recognized as critical for understanding the trajectory of the HIV epidemic and planning and monitoring an effective response, especially for countries with concentrated and low epidemics such as those in Asia. Context:To help countries estimate population sizes of key populations, global guidelines were updated in 2011 to reflect new technical developments and recent field experiences in applying these methods. Action:In September 2013, a meeting of programme managers and experts experienced with population size estimates (PSE) for key populations was held for 13 Asian countries. This article summarizes the key results presented, shares practical lessons learnt and reviews the methodological approaches from implementing PSE in 13 countries. Lessons learnt:It is important to build capacity to collect, analyse and use PSE data; establish a technical review group; and implement a transparent, well documented process. Countries should adapt global PSE guidelines and maintain operational definitions that are more relevant and useable for country programmes. Development of methods for non-venue-based key populations requires more investment and collaborative efforts between countries and among partners.

Health access livelihood framework reveals potential barriers in the control of schistosomiasis in the Dongting Lake area of Hunan Province, China.

BACKGROUND: Access to health care is a major requirement in improving health and fostering socioeconomic development. In the People's Republic of China (P.R. China), considerable changes have occurred in the social, economic, and health systems with a shift from a centrally planned to a socialist market economy. This brought about great benefits and new challenges, particularly for vertical disease control programs, including schistosomiasis. We explored systemic barriers in access to equitable and effective control of schistosomiasis. METHODOLOGY: Between August 2002 and February 2003, 66 interviews with staff from anti-schistosomiasis control stations and six focus group discussions with health personnel were conducted in the Dongting Lake area, Hunan Province. Additionally, 79 patients with advanced schistosomiasis japonica were interviewed. The health access livelihood framework was utilized to examine availability, accessibility, affordability, adequacy, and acceptability of schistosomiasis-related health care. PRINCIPAL FINDINGS: We found sufficient availability of infrastructure and human resources at most control stations. Many patients with advanced schistosomiasis resided in non-endemic or moderately endemic areas, however, with poor accessibility to disease-specific knowledge and specialized health services. Moreover, none of the patients interviewed had any form of health insurance, resulting in high out-of-pocket expenditure or unaffordable care. Reports on the adequacy and acceptability of care were mixed. CONCLUSIONS/SIGNIFICANCE: There is a need to strengthen health awareness and schistosomiasis surveillance in post-transmission control settings, as well as to reduce diagnostic and treatment costs. Further studies are needed to gain a multi-layered, in-depth understanding of remaining barriers, so that the ultimate goal of schistosomiasis elimination in P.R. China can be reached.

How are countries in the Western Pacific Region tracking the HIV epidemic? Results from a 2011 survey of ministries of health.

In 2011, as part of the World Health Organization global reporting tool to collect data on the progress of improving the health sector response to HIV/AIDS towards universal access, a questionnaire was sent to ministries of health of Western Pacific Region Member States on the scope and functioning of their HIV surveillance systems. Of the 17 countries that responded, 13 were low- to middle-income countries and four were high-income countries. Regular serosurveillance surveys are conducted with female sex workers in all lower- and middle-income countries that responded to the survey but less so with people who inject drugs and men who have sex with men. Furthermore, there are no surveillance activities of the key populations in most of the Pacific island countries. It is recommended that estimations of high-risk populations be conducted in priority Pacific island countries and tailored surveillance systems be designed. Efforts should also be made to gather and accumulate data from sufficient geographic coverage to allow the HIV epidemic to continue to be monitored.

Experience in piloting HIV drug resistance early warning indicators to improve the antiretroviral program in Papua New Guinea.

In 2009, World Health Organization human immunodeficiency virus drug resistance early warning indicator monitoring was piloted at 2 large antiretroviral therapy (ART) clinics in Papua New Guinea: Heduru Clinic in Port Moresby and Tininga Clinic in Mount Hagen. Results demonstrated that both Heduru and Tininga clinics met internationally suggested targets for prescribing appropriate first-line ART regimens in accordance with national ART guidelines, retention on first-line ART at 12 months, and drug supply continuity. However, both clinics failed to achieve suggested targets for rates of loss to follow-up and on-time pill pickup. Reasons for poor clinic performance on loss to follow-up and on-time pill pickup were explored, and appropriate corrective actions were implemented.

How are countries in the Western Pacific Region tracking the HIV epidemic? Results from a 2011 survey of ministries of health

In 2011, as part of the World Health Organization global reporting tool to collect data on the progress of improving the health sector response to HIV/AIDS towards universal access, a questionnaire was sent to ministries of health of Western Pacific Region Member States on the scope and functioning of their HIV surveillance systems. Of the 17 countries that responded, 13 were low- to middle-income countries and four were high-income countries. Regular serosurveillance surveys are conducted with female sex workers in all lower- and middle-income countries that responded to the survey but less so with people who inject drugs and men who have sex with men. Furthermore, there are no surveillance activities of the key populations in most of the Pacific island countries. It is recommended that estimations of high-risk populations be conducted in priority Pacific island countries and tailored surveillance systems be designed. Efforts should also be made to gather and accumulate data from sufficient geographic coverage to allow the HIV epidemic to continue to be monitored.

HIV drug resistance assessment in the Western Pacific region. A systematic review.

Antiretroviral therapy is being rapidly scaled-up in Western Pacific region countries. Prevention and assessment of HIV drug resistance is an essential component of successful global antiretroviral therapy scale-up. We performed a systematic review of public health surveys and HIV drug resistance studies conducted in the low- and middle-income countries in the Western Pacific region. A total of 38 publications assessing HIV drug resistance were reviewed. Studies assessing transmitted drug resistance in recently infected individuals or drug resistance among individuals starting antiretroviral therapy found low rates of HIV drug resistance. Assessments of HIV drug resistance emerging in populations receiving antiretroviral therapy demonstrated variable rates of drug resistance, but suggest an urgent need to support antiretroviral therapy adherence and retention in care, ensure the use of quality assured drugs, and guarantee continuous drug supplies. Additionally, programmatic assessment informed by routine standardized surveillance of transmitted and acquired HIV drug resistance is essential to optimize antiretroviral therapy delivery in the Western Pacific region.

Investment in HIV/AIDS programs: does it help strengthen health systems in developing countries?

BACKGROUND: There is increasing debate about whether the scaled-up investment in HIV/AIDS programs is strengthening or weakening the fragile health systems of many developing countries. This article examines and assesses the evidence and proposes ways forward. DISCUSSION: Considerably increased resources have been brought into countries for HIV/AIDS programs by major Global Health Initiatives. Among the positive impacts are the increased awareness of and priority given to public health by governments. In addition, services to people living with HIV/AIDS have rapidly expanded. In many countries infrastructure and laboratories have been strengthened, and in some, primary health care services have been improved. The effect of AIDS on the health work force has been lessened by the provision of antiretroviral treatment to HIV-infected health care workers, by training, and, to an extent, by task-shifting. However, there are reports of concerns, too - among them, a temporal association between increasing AIDS funding and stagnant reproductive health funding, and accusations that scarce personnel are siphoned off from other health care services by offers of better-paying jobs in HIV/AIDS programs. Unfortunately, there is limited hard evidence of these health system impacts. Because service delivery for AIDS has not yet reached a level that could conceivably be considered "as close to Universal Access as possible," countries and development partners must maintain the momentum of investment in HIV/AIDS programs. At the same time, it should be recognized that global action for health is even more underfunded than is the response to the HIV epidemic. The real issue is therefore not whether to fund AIDS or health systems, but how to increase funding for both. SUMMARY: The evidence is mixed - mostly positive but some negative - as to the impact on health systems of the scaled-up responses to HIV/AIDS driven primarily by global health partnerships. Current scaled-up responses to HIV/AIDS must be maintained and strengthened. Instead of endless debate about the comparative advantages of vertical and horizontal approaches, partners should focus on the best ways for investments in response to HIV to also broadly strengthen the primary health care systems.

School-based interventions to enhance knowledge and improve case management of schistosomiasis: a case study from Hunan, China.

This paper discusses an intersectoral health-related intervention, using cartoons and video-recording, print materials and face-to-face educational methods, to increase children's knowledge of schistosomiasis, which in turn might improve the case management of early diagnosis and treatment. The main components of the project were (i) the collaboration between the departments of public health and education and (ii) a randomized, controlled, school-based field trial conducted in the Dongting Lake region, China. Children in the experimental group (n=604) and their parents participated in the educational programme. Control children (n=527) received a 2 hour lecture about the disease. All participants were pre-tested, and retested five months after the conduct of the educational intervention. The results show significant changes among children and their parents in the experimental group related to knowledge about schistosomiasis and beliefs towards screening and treatment of the disease. Children in the experimental group also had better compliance than children in the control group for regular screening for schistosomiasis. These findings indicate that carefully designed education programmes are useful for providing both children and their families with information about the prevention and treatment of schistosomiasis. Intersectoral collaboration holds promise to deliver research-based interventions for enhanced knowledge of schistosomiasis and improved case management.