Weekend Research Reads #2

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This weekend’s research reads is really heavy on the antibiotic/antimicrobial resistance head because the BMJ published a special issue on AMR in South East Asia.

Antimicrobial/Antibiotic Resistance

1. Antibiotic resistome promotion in drinking water during biological activated carbon treatment: Is it influenced by quorum sensing?


  • Antibiotic resistome promotion was observed after drinking water biological activated carbon treatment.
  • 29 antibiotic resistance genes were identified as biofilm source and persisted in drinking water.
  • Shift of bacterial communities was identified as key factor driving ARGs alteration.
  • Acyl Homoserine Lactones promoted horizontal gene transfer in intragenus mating systems.


The contamination of antibiotic resistance genes (ARGs) in drinking water may pose a direct threat to human health. This study applied high-throughput qPCR and sequencing to investigate the dynamics of ARGs and bacterial communities during the advanced treatment of drinking water using biological activated carbon. The promotion of ARGs was observed, and the normalized copy number of ARGs increased significantly after BAC treatment, raising the number of detected ARGs from 84 to 159. Twenty-nine ARGs were identified as biofilm-influencing sources in the BAC, and they persisted after chlorination. The shift of bacterial communities primarily had effects on the changes in resistome. Firmicutes, Cyanobacteria were related to persistent ARGs mostly in the BAC biofilm. Meanwhile, the Acyl-Homoserine Lactones (AHLs), quorum sensing molecules, and bacteria that produced AHLs were identified to understand the promotion of ARGs. The isolated AHL-producing bacteria belonged to the Proteobacteria, Firmicutes and Bacteroidetes phyla. Six detectable AHLs had an influence on plasmid-based horizontal gene transfer in the intragenus mating systems, indicating that the dynamics of ARGs were strongly affected by quorum sensing between specific bacteria in the biofilm. These results provide new insight into the mechanism of antibiotic resistome promotion in BAC biofilms.

2. Antibiotic resistance genes in an urban river as impacted by bacterial community and physicochemical parameters


Antibiotic resistance genes (ARGs) in urban rivers are a serious public health concern in regions with poorly planned, rapid development. To gain insights into the predominant factors affecting the fate of ARGs in a highly polluted urban river in eastern China, a total of 285 ARGs, microbial communities, and 20 physicochemical parameters were analyzed for 17 sites. A total of 258 unique ARGs were detected using high-throughput qPCR, and the absolute abundance of total ARGs was positively correlated with total organic carbon and total dissolved nitrogen concentrations (P < 0.01). ARG abundance and diversity were greatly altered by microbial community structure. Variation partitioning analysis showed that the combined effects of multiple factors contributed to the profile and dissemination of ARGs, and variation of microbial communities was the major factor affecting the distribution of ARGs. The disparate distribution of some bacteria, including Bacteroides from mammalian gastrointestinal flora, Burkholderia from zoonotic infectious diseases, and Zoogloea from wastewater treatment, indicates that the urban river was strongly influenced by point-source pollution. Results imply that microbial community shifts caused by changes in water quality may lead to the spread of ARGs, and point-source pollution in urban rivers requires greater attention to control the transfer of ARGs between environmental bacteria and pathogens.

Antibiotic resistance genes (ARGs) are globally prevalent in mariculture sediment, and their presence is an issue of concern in the context of antibiotic use. Although large amounts of fishmeal have been released into the sediment, the role of fishmeal in ARG dissemination remains unclear. In this study, high-throughput ARG profiles in representative fishmeal products and the impact of fishmeal on the sediment resistome were investigated. A total of 132 unique ARGs and 4 mobile genetic elements (MGEs) were detected in five fishmeal products. ARG abundance and diversity in the mariculture microcosm sediment were significantly increased by the addition of fishmeal, and trends in ARG patterns correlated with the resident bacterial community in sediment (P < 0.05). After DNase treatment of fishmeal removed 84.3% of total ARGs, the remaining nutrients in fishmeal increased the relative abundance but not the diversity of ARGs in microcosm sediment. Our study has revealed for the first time that fishmeal itself is a major reservoir for ARGs, and the shift in the bacterial community induced by the nutrients in fishmeal is the main driver shaping the resistome in mariculture microcosm sediment. Our findings caution against the previously unperceived risk of ARG propagation in fishmeal-receiving ecosystems.



Resistance of Staphylococcus aureus to commonly used antibiotics is linked to their ability to acquire and disseminate antimicrobial-resistant determinants in nature, and the marine environment may serve as a reservoir for antibiotic-resistant bacteria. This study determined the antibiotic sensitivity profile of S.aureus isolated from selected beach water and intertidal beach sand in the Eastern Cape Province of South Africa.
Two hundred and forty-nine beach sand and water samples were obtained from 10 beaches from April 2015 to April 2016. Staphylococcus aureus was isolated from the samples using standard microbiological methods and subjected to susceptibility testing to 15 antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) was detected by susceptibility to oxacillin and growth on Brilliance MRSA II agar. Antibiotic resistance genes including mecA, femrpoB, blaZ, ermB, ermA, ermC, vanA, vanB, tetK andtetM were screened.
Thirty isolates (12.3%) were positive for S. aureus by PCR with over 50% showing phenotypic resistance to methicillin. Resistance of S. aureus to antibiotics varied considerably with the highest resistance recorded to ampicillin and penicillin (96.7%), rifampicin and clindamycin (80%), oxacillin (73.3%) and erythromycin (70%). S. aureus revealed varying susceptibility to imipenem (96.7%), levofloxacin (86.7%), chloramphenicol (83.3%), cefoxitin (76.7%), ciprofloxacin (66.7%), gentamycin (63.3%), tetracycline and sulfamethoxazole-trimethoprim (56.7%), and vancomycin and doxycycline (50%). All 30 (100%) S. aureusisolates showed multiple antibiotic-resistant patterns (resistant to three or more antibiotics). The mecA, femA,rpoB, blaZ, ermB and tetM genes were detected in 5 (22.7%), 16 (53.3%), 11 (45.8%), 16 (55.2%), 15 (71.4%), and 8 (72.7%) isolates respectively.

Results from this study indicate that beach water and sand from the Eastern Cape Province of South Africa may be potential reservoirs of antibiotic-resistant S. aureuswhich could be transmitted to exposed humans and animals.

5. Impact of a mixed educational and semi-restrictive antimicrobial stewardship project in a large teaching hospital in Northern Italy



The overuse of antimicrobials favors the dissemination of antimicrobial resistance, as well as invasive fungal diseases and Clostridium difficile infections (CDI). In this study, we assessed the impact of a mixed educational and semi-restrictive antimicrobial stewardship (AMS) project in a large teaching hospital in Italy.


The AMS project was conducted from May 2014 to April 2016. It consisted of two initiatives in two consecutive periods: (1) educational activities; (2) semi-restrictive control of antimicrobial prescribing through a computerized software. The primary endpoint was consumption of antibacterials and antifungals. Secondary endpoints were incidence of CDI, methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI), carbapenem-resistant Klebsiella pneumoniae (CRKP) BSI, and Candida BSI.


During the study period, a statistically significant reduction in consumption was observed for antibacterials (−1.45 defined daily doses (DDD)/1000 patient-days monthly, 95% confidence intervals [CI] −2.38 to −0.52, p 0.004), mainly driven by reductions in the use of fluoroquinolones, third/fourth generation cephalosporins, and carbapenems. No decrease in consumption of antifungals was observed (−0.04 DDD/1000 patient-days monthly, 95% CI −0.34 to +0.25, p 0.750). A statistically significant trend towards reduction was observed for incidence of CRKP BSI (incidence rate ratio 0.96, 95% CI 0.92–0.99, p 0.013). No statistically significant variations in trends were observed for CDI, MRSA BSI, and Candida BSI.


The mixed AMS project was effective in reducing the use of major antibacterials and the incidence of CRKP BSI. Further research is needed to assess the extent of long-term benefits of semi-restrictive approaches.

Antimicrobials represent one of humanity’s medical revolutions enabling us to treat both human and veterinary bacterial infections. It is therefore of utmost importance to preserve their effectiveness. However, during the last decades the continuing rapid development of antimicrobial resistance (AMR) has emerged as a major global public health concern (1). Resistant bacteria may hamper the treatment of infections resulting in prolonged illness, disability, and death (2).

In veterinary medicine, antimicrobials play a crucial role in the maintenance of animal health, animal welfare and food-safety (3). However, a not yet quantifiable share of the burden of resistance for public health is attributable to the use of antimicrobials in livestock production (4–6). Farm animals are exposed to considerable quantities of antimicrobials (7) and can act as an important reservoir of AMR genes, which could be transmitted to humans through the food chain, direct animal contact and the environment. Use of antimicrobials in agriculture also includes those defined by the World Health Organization (WHO) as “critically important” for human medicine (8). Resistance against these substances can limit dramatically the treatment options against serious human bacterial diseases. Notorious examples include the vancomycin resistant (VRE) enterococci, the extended-spectrum β-lactamase (ESBL) producing Enterobacteriaceae and the recently detected plasmid-mediated colistin resistance (mcr-1 gene) in livestock, food and humans in China (9–11).

7. Association between selected antimicrobial resistance genes and antimicrobial exposure in Danish pig farms.


Bacterial antimicrobial resistance (AMR) in pigs is an important public health concern due to its possible transfer to humans. We aimed at quantifying the relationship between the lifetime exposure of antimicrobials and seven antimicrobial resistance genes in Danish slaughter pig farms. AMR gene levels were quantified by qPCR of total-community DNA in faecal samples obtained from 681 batches of slaughter pigs. The lifetime exposure to antimicrobials was estimated at batch level for the piglet, weaner, and finisher periods individually for the sampled batches. We showed that the effect of antimicrobial exposure on the levels of AMR genes was complex and unique for each individual gene. Several antimicrobial classes had both negative and positive correlations with the AMR genes. From 10-42% of the variation in AMR gene levels could be explained in the final regression models, indicating that antimicrobial exposure is not the only important determinant of the AMR gene levels.

7. Risk assessment for antibiotic resistance in South East Asia

Fanny Chereau and colleagues assess the risk of the emergence and spread of antibiotic resistance in South East Asia and suggest it is the highest of the World Health Organization regions

Key messages

  • South East Asia is at high risk of the emergence and spread of antibiotic resistance in humans

  • The risk assessment framework can help countries identify interventions for maximum impact, although isolated interventions will be inadequate

  • A comprehensive strategy using the One Health approach is needed to contain antibiotic resistance in South East Asia

8. Antibiotic resistance and its containment in India

Manish Kakkar and colleagues discuss factors contributing to antibiotic resistance in India, and examine policy initiatives to address it

Antibiotic resistance is a major public health threat in India. A high burden of infectious diseases, unregulated sale of antibiotics, financial incentives for healthcare providers to prescribe antibiotics, patient expectations, rising incomes, and limited public health response have helped drive the emergence of resistance.1 Resistance patterns in India in human samples are shown in box 1. Resistance to commonly used antibiotics is increasing. This complicates clinical management, and newer, more expensive antibiotics need to be used. Resistance to newer, broad spectrum drugs such as carbapenems, which are the antibiotics of last resort, has been seen in parallel with their increased use.4

Cecilia Stålsby Lundborg and Ashok Tamhankar discuss how antibiotic residues in the environment contribute to antibiotic resistance in South East Asia and propose actions to mitigate the problem

The global action plan on antimicrobial resistance1 emphasises the One Health approach—seeing humans, animals, the food chain, the environment, and the interconnectedness between them as one entity. With growing economic development in South East Asia, the production and use of antibiotics—and therefore also their residues in the environment—are expected to increase.

Antibiotic residues in the environment lead to resistant bacteria through selective pressure. Antibiotics like fluoroquinolones (for example, ciprofloxacin) and sulphonamides, (such as sulfamethoxazole) are chemically stable. Their residues are often detected in the environment, and resistance to them is frequently reported.23 Beta-lactam antibiotics produce readily degradable residues that are not easily detected but still contribute to resistance.23Theoretically, a chance interaction between a single molecule of an antibiotic and a bacterium can trigger natural selection for resistance, or a mutation favouring resistance. Subsequently, a vertical gene transfer (from one generation to another) or a horizontal gene transfer (transfer of resistance genes from one bacterium to another through a plasmid) may occur (fig 1). Identification of a complete identical sequence of antibiotic resistance genes from soil bacteria and clinical pathogens has demonstrated the potential for horizontal gene transfer between environmental antibiotic resistant bacteria and pathogenic bacteria.2 Humans may be exposed to antibiotic residues or directly to antibiotic resistant bacteria, including pathogens, through food or environment, and potentially be infected. Reduced effectiveness of antibiotics may result in prolonged or poorly controlled infections.

Aparna Shah and colleagues call on South East Asian countries to invest in national networks of laboratories for robust and standardised surveillance of antimicrobial resistance

Key messages

  • Poor infrastructure of laboratories affects surveillance of AMR in South East Asia

  • Developing national networks of laboratories for AMR surveillance is a priority

  • Standard protocols for measuring and reporting resistance must be followed

The patterns and driving forces for the emergence and spread of antimicrobial resistance (AMR) vary from place to place. Monitoring local resistance patterns helps implement targeted measures to contain AMR and to treat infections effectively. Laboratories are important for quantifying the burden of AMR and resistance patterns, and it is vital they follow standard protocols to generate quality data. Collating local data on AMR is essential to obtain a representative picture of national trends, plan and measure the effect of policies and interventions, and contribute to the understanding of AMR at a regional and global level.

In 2011 health ministers of South East Asian countries released the Jaipur declaration, signifying their commitment to work together to contain AMR.1 The declaration emphasises the need to increase capacity and share best practices for laboratory based surveillance of AMR and foster the effective use of data to modify antibiotic policy.

11. Antimicrobial resistance communication activities in South East Asia

There is an urgent need to raise public awareness of antimicrobial resistance in the region, say Natasha Godinho and colleagues

Public health communication is the scientific development, strategic dissemination, and critical evaluation of relevant, accurate, accessible, and understandable health information, communicated to and from intended audiences to advance the health of the public. In the field of antimicrobial resistance (AMR), evidence from developed countries1 2 shows that effective communication campaigns contribute towards raising the discourse around AMR and in promoting the rational use of antibiotics by prescribers and patients, as well as within the agriculture and food industries.

Our research shows, however, that there is a limited volume of information available on AMR related communication campaigns in the World Health Organization South East Asia Region (SEAR). All countries in the region need to adopt comprehensive, strategic communication campaigns to transform behaviours that lead to antimicrobial resistance. This article describes the landscape of government led public awareness interventions on AMR in South East Asia, and suggests recommendations to help national level authorities in the development of future campaigns.

Sirenda Vong and colleagues argue that investing in information technology surveillance systems to detect trends is an essential first step in tackling antimicrobial resistance in South East Asian countries

Key messages

  • Lack of information technology (IT) infrastructure is often cited as a barrier to comprehensive antimicrobial resistance (AMR) surveillance and antibiotic usage stewardship programmes in low and middle income countries

  • Few open access software options that might support an IT infrastructure for AMR surveillance are available

  • IT systems should support regular communication between central and local levels to enable feedback, improved data quality, and acceptance by users

  • Good data quality in an IT system requires data validation to be carried out in collaboration with the laboratories to correct inconsistencies and errors

  • The World Health Organization, South East Asia regional office will support international partners to translate the present recommendations into actions and mobilise resources and leverage partnerships

13. New chapter in tackling antimicrobial resistance in Thailand

Nithima Sumpradit and colleagues describe the experience of Thailand in developing its national strategic plan on antimicrobial resistance and highlight the need for sustained political commitment and multisectoral collaboration

Antimicrobial resistance (AMR) is a serious global health threat which can cross borders and human and animal species. Concerted action is required at global, regional and national levels to tackle it. The World Health Assembly adopted the global action plan on AMR in 2015, which called on member states of the World Health Organization to develop national action plans by May 2017.1 To date, 67 member states have finalised their national action plans.

AMR places a high burden on health and the economy in Thailand,2 and the government has shown strong political commitment to tackle AMR over the past decade. Box 1 summarises the effect of AMR and antimicrobial consumption in Thailand.

A pilot programme to evaluate Indonesia’s antimicrobial resistance containment plan shows that progress is on the right track, but substantial strengthening is needed, say Harry Parathon and colleagues

Key messages

  • A national action plan to combat antimicrobial resistance (AMR) in line with the Global Action Plan was finalised and shared with WHO before the WHO General Assembly in May 2017

  • Indonesia’s programme to contain AMR is in the early phase of implementation based on the situation analysis tool produced by the South East Asia Regional Office of WHO

  • A substantial achievement of the programme in the past year was the provision of considerable national funds to support national activities to combat AMR

  • Indonesia’s health authorities recognised many major challenges including setting up a strong governance that incorporates a multisectoral collaboration and coordination, national surveillance of AMR and enforcement of policies for rational use of antibiotics and AMR stewardship

15. Developing a situation analysis tool to assess containment of antimicrobial resistance in South East Asia

Manish Kakkar and colleagues discuss the development of a tool to assess how programmes tackling antimicrobial resistance in South East Asia are faring

Key messages

  • The situation analysis tool can assess and monitor the progress made towards implementing the national action plan for antimicrobial resistance in the member states of the South East Asia region

  • A multi-stakeholder review, conducted through guided discussions, table top exercises, and site visits as needed identifies strengths, challenges, and implementation gaps

  • The tool has been developed in the context of developing countries with rudimentary or non-existent programmes for the containment of antimicrobial resistance

16. Risk assessment for antibiotic resistance in South East Asia

Fanny Chereau and colleagues assess the risk of the emergence and spread of antibiotic resistance in South East Asia and suggest it is the highest of the World Health Organization regions

Key messages

  • South East Asia is at high risk of the emergence and spread of antibiotic resistance in humans

  • The risk assessment framework can help countries identify interventions for maximum impact, although isolated interventions will be inadequate

  • A comprehensive strategy using the One Health approach is needed to contain antibiotic resistance in South East Asia

17. Drug resistance in malaria, tuberculosis, and HIV in South East Asia: biology, programme, and policy considerations

Malaria, tuberculosis, and HIV present unique challenges in the control of antimicrobial resistance, and require targeted policies, say Samiran Panda and colleagues

The World Health Organization South East Asia region, home to a third of the world’s population, has half the global incident cases of tuberculosis (TB), and a tenth of the estimated burden of malaria and HIV.1 The risk of disease transmission from travel and migration of people from and within the region highlight the importance of tackling this large disease burden. Failure to control or eliminate these diseases could negatively affect health and development worldwide. The increasing resistance to the drugs used to treat malaria, TB, and HIV2 (fig 1), and its ability to move across national borders, are challenges to controlling these diseases. Furthermore, drug resistance in malaria, TB, and HIV, and the effect of individual, sociocultural, environmental, and political factors differ between countries, which make containment even harder.

18. Antimicrobial policy interventions in food animal production in South East Asia

Flavie Goutard and colleagues call for concerted multisectoral measures through stronger policies to combat antimicrobial resistance

Key messages

  • Key policies for tackling antimicrobial resistance are still lacking in many countries in the South East Asia region, including veterinary surveillance of antimicrobial resistance and antimicrobial use, raising awareness among professionals and farmers, and strengthening the national drug regulatory authorities in the animal health sector

  • Although bans on over-the-counter antibiotics and use of antibiotics as growth promoters have been introduced in many countries, enforcement remains a challenge

  • Further evidence is needed to understand local barriers and to propose viable, policy driven solutions

  • The World Health Organization, World Organisation for Animal Health, and the Food and Agriculture Organization have important roles in identifying best practices in the region to support development of national policies

Health Policy/Global Health

1. Framework legislation for non-communicable diseases: and for the Sustainable Development Goals?


‘Framework legislation’ refers to legislation that sets out structures for governance and accountability or other processes for guiding the decisions and actions taken by government or the executive. Framework legislation for non-communicable diseases (NCDs) provides the opportunity for countries to focus their political commitment, to set national targets, and a time-frame for achieving them, and to create cross-sectoral governance structures for the development and implementation of innovative policies. Although they extend well beyond NCDs, the health-related Sustainable Development Goals (SDGs) create similar demands for effective national governance. A similar case might, therefore, be made for framework legislation for the health-related SDGs or for legislation to govern particular aspects, such as managing commercial relationships with the private sector or managing conflicts of interest. This article considers the possible benefits of framework legislation, including what issues might be appropriate for inclusion in a framework law. The absence of framework legislation should neither be seen as an excuse for inaction, nor is framework legislation a substitute for detailed regulation of areas such as sanitation and water quality, tobacco and alcohol control, food safety, essential medicines or poisons. The ultimate test for framework legislation will be its capacity to provide a catalyst for action and to accelerate progress towards national and global health goals.

Key questions

What is already known about this topic?

  • Heads of state made a number of time-bound commitments at the high-level meeting of the United Nations (UN) General Assembly on non-communicable diseases in 2014. These included commitments to set national targets and process indicators for 2025 and to consider strengthening national multisectoral plans and policies.

  • In 2014, members of the UN General Assembly adopted the Sustainable Development Goals. The health-related goals and targets represent an ambitious plan for advancing global health for the period 2015–2030.

What are the new findings?

  • ‘Framework legislation’ refers to legislation that establishes structures or processes to guide future actions and decisions by governments or the executive.

  • Framework legislation for non-communicable diseases (NCDs) provides the opportunity for countries to focus their political commitment, to set national targets and to create cross-sectoral governance structures for the development and implementation of innovative policies. Although they are broader than NCDs, the health-related Sustainable Development Goals impose similar demands on countries for effective national governance.

Recommendations for policy

  • While the absence of legislation is not an excuse for inaction, framework legislation may contribute to the effective coordination of national responses to non-communicable diseases (NCDs) and to the health-related Sustainable Development Goals and targets.

  • Framework legislation is not a substitute for detailed legislation governing tobacco, alcohol, food, poisons, essential medicines and other areas. Nevertheless, framework legislation has the potential to accelerate national progress by raising the political profile of NCDs, clarifying who is accountable for taking action and coordinating a cross-sectoral response.

  • Alternatively, government may consider more limited legislation; for example, to manage commercial relationships with the private sector or to manage conflicts of interest.

2. Universal health coverage, economic slowdown and system resilience: Africa’s policy dilemma

Summary box

  • Achieving universal health coverage (UHC) has become a dominant global health policy preoccupation during the last decade, advocating ambitious healthcare coverage goals, increases in health funding and financial pooling mechanisms for social protection;

  • As many commodity-dependent African economies are presently experiencing a marked slowdown and international assistance is becoming more volatile, there seems to be a growing divide between UHC principles and policy-makers’ everyday concerns in the field;

  • In order to keep inspiring health development in Africa, UHC thinking and international health support need to take into account the continent’s non-linear growth pattern and the need to ensure that its health systems are resilient to external shocks;

  • Drawing from past mistakes and from the continent’s reaction to past crises, a number of macro, meso and micro policies can be identified to strengthen the UHC concept, and reconcile its aspirations with Africa’s current economic outlook.

3. The ethics of setting national antibiotic policies using financial incentives


Antimicrobial resistance (AMR) is an increasingly urgent global public health issue. Data from Public Health England — from the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) — quantifies the scale of antibiotic resistance in key bacterial pathogens.

The Department of Health’s 5-year strategy to reduce morbidity and mortality associated with AMR (2013–2018) focused on optimising antibiotic prescribing and improving infection prevention and control.1 In April 2015 NHS England introduced a Quality Premium (QP) focusing on reducing antibiotics. QPs are financial rewards, with a maximal value equivalent to £5 per patient, intended to reward clinical commissioning groups (CCGs) for improvements in the quality of the services that they commission and for associated improvements in health outcomes and reducing inequalities. The AMR QP provided commissioners with financial incentives to reduce antibiotic prescribing; 80% were linked to primary care quality measures (reduction in absolute number of antibiotic prescriptions by 1%, decrease in use of broad spectrum antibiotics by 10%) and 20% linked to improving availability of antibiotic prescribing data from secondary care.2


Incentives are a tool that governments use to help support behaviour change, are a recognised domain in behaviour change methodology, and can be considered a form of trade. CCGs are offered an incentive in the form of additional funds for investment if they have reduced antibiotic prescribing. However, the CCG also has to show that it manages public funds responsibly and will only receive a QP if it has managed its funds according to the ‘Managing Public Money’ guidelines and does not require financial support during the financial year (nor deviate substantially from expected surpluses/deficits).2

In 2014/2015 only 27% of the total available QP was achieved by CCGs. Although the financial incentive is directed towards CCGs, the behavioural change being targeted is at the level of …

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Health technology assessment (HTA) is widely viewed as an essential component in good universal health coverage (UHC) decision-making in any country. Various HTA tools and metrics have been developed and refined over the years, including systematic literature reviews (Cochrane), economic modelling, and cost-effectiveness ratios and acceptability curves. However, while the cost-effectiveness ratio is faithfully reported in most full economic evaluations, it is viewed by many as an insufficient basis for reimbursement decisions. Emotional debates about the reimbursement of cancer drugs, orphan drugs, and end-of-life treatments have revealed fundamental disagreements about what should and should not be considered in reimbursement decisions. Part of this disagreement seems related to the equity-efficiency tradeoff, which reflects fundamental differences in priorities. All in all, it is clear that countries aiming to improve UHC policies will have to go beyond the capacity building needed to utilize the available HTA toolbox. Multi-criteria decision analysis (MCDA) offers a more comprehensive tool for reimbursement decisions where different weights of different factors/attributes can give policymakers important insights to consider. Sooner or later, every country will have to develop their own way to carefully combine the results of those tools with their own priorities. In the end, all policymaking is based on a mix of facts and values.

Cholera/Enteric Diseases

1. Cholera in Niger Republic: An Analysis of National Surveillance Data, 1991 – 2015



Cholera is an infectious disease caused by a gram negative bacteria, Vibrio cholerae. It was found for the first time in Niger during year 1970 and continues to occur as an issue of major public health importance.


This study aimed at more accurately defining the burden of cholera in Niger.


Cholera surveillance data from the direction of epidemy surveillance and response reported to the Niger ministry of public health and the world health organization were reviewed and analyzed to determine trends in cholera disease.


Of Niger’s 8 regions or states, 7 were very active in reporting cases each year between 1991 and 2015. Globally, cholera cases and deaths were 26,835 and 1,430, respectively (CFR = 5.3%).


Taken together, the epidemiological trends of cholera in Niger showed annual increase in frequency and length of outbreaks during the 21 years under review. To successfully reduce the burden of cholera outbreaks in Niger, concerted efforts by the government and non-government organizations as development partners through longterm investments are urgently needed to strengthen preventive measures for early detection and confirmation of cases, followed by a well-coordinated, timely, and effective response.

2. The impact of prevention and control of infectious disease law on diarrhoea control: a 5-year evaluation in multiple provinces in Vietnam


To address to burden of infectious diseases such as diarrhoea, the Vietnamese government has enacted the Law on Prevention and Control of Infectious Diseases (LPCIDs) since July 2008. However, no evaluation of the impact of the LPCID has been conducted. This study aims to evaluate the impact of the LPCID on diarrhoeal control for the 5 years following the implementation of LPCID in Vietnam. We used an interrupted time series design using a segmented regression analysis to estimate the ‘province-level’ impact of LPCID and then used random-effect meta-analysis to estimate the pooled effect sizes of the ‘country-level’ impact of LPCID on diarrhoeal control throughout Vietnam. The results show that the impacts varied by provinces. They were classified in four groups: ‘positive impact, positive impact without sustainability, possibly positive impact, no or negative impact’ of the LPCID. The meta-analysis indicated that the country-level impact of the LPCID became significant at 11 months after the LPCID took effect, with a decrease in level of diarrhoea of 9.7% (coefficient, −0.097; 95% CI: −19.1 to − 0.002) and a permanent downward trend of diarrhoea at a rate of 1.1% per month (coefficient, −0.011; 95% CI: −0.02 to − 0.003); whereas the trend in diarrhoea before the LPCID took effect was unchanging (coefficient, 0.002; 95% CI, 0–0.004). At 12, 24, 36, 48 and 60 months following the LPCID implementation date the levels of diarrhoea decreased by 10.9% (coefficient, −0.109; 95% CI: −0.203 to − 0.015), P < 0.01), 21.8% (coefficient, −0.218; 95% CI: −0.338 to − 0.098), P < 0.01), 31% (coefficient, −0.31; 95% CI: −0.474 to − 0.145), P < 0.01), 46.8% (coefficient, −0.468; 95% CI: −0.667 to − 0.27), P < 0.01), 48.2% (coefficient, −0.482; 95% CI: −0.708 to − 0.256), P < 0.01) respectively. The findings of this study reveal the effectiveness of the LPCID in reducing diarrhoea incidence in Vietnam. However, further studies should be conducted to better understanding the cost-effectiveness, acceptability, and sustainability of each component of the LPCID.

Zoonoses/One Health

1. Rift Valley Fever: Does Wildlife Play a Role?


Rift Valley fever (RVF) virus (RVFV) is an emerging vector-borne pathogen that causes sporadic epizootics and epidemics with multi-year, apparently quiescent, inter-epidemic periods. The epidemiology and ecology of the virus during these inter-epidemic periods is poorly understood. There is evidence for low-level circulation of the virus in livestock and wild ruminants; however, as of yet there is no evidence to identify a specific mammalian reservoir host. Using a systematic approach, this review synthesizes results from serosurveys, attempts at viral detection, and experimental infection of wildlife. These data demonstrate there is a gap in research conducted on RVF in wild ruminants. Specifically, there is very little published data on the pathogenicity of an RVFV infection in various wildlife species, validation of diagnostic assays for exposure to RVFV and understanding of epizootic or endemic disease dynamics in wild ruminants. We recommend that future research on RVFV incorporate a more systematic approach to understand the low-level cycling of the virus during inter-epidemic periods in both wild and domestic ruminant species.



Dengue is a vector-borne disease transmitted by Aedes mosquitoes. It is considered an important public health problem in many countries worldwide. However, only a few studies have been conducted on primates and domestic animals that could potentially be a reservoir of dengue viruses. Since domestic dogs share both habitats and vectors with humans, this study aimed to investigate whether domestic dogs living in different ecological settings in dengue endemic areas in Thailand could be naturally infected with dengue viruses.

Methodology/Principal findings

Serum samples were collected from domestic dogs in three different ecological settings of Thailand: urban dengue endemic areas of Nakhon Sawan Province; rubber plantation areas of Rayong Province; and Koh Chang, an island tourist spot of Trat Province. These samples were screened for dengue viral genome by using semi-nested RT-PCR. Positive samples were then inoculated in mosquito and dog cell lines for virus isolation. Supernatant collected from cell culture was tested for the presence of dengue viral genome by semi-nested RT-PCR, then double-strand DNA products were double-pass custom-sequenced. Partial nucleotide sequences were aligned with the sequences already recorded in GenBank, and a phylogenetic tree was constructed. In the urban setting, 632 domestic dog serum samples were screened for dengue virus genome by RT-PCR, and six samples (0.95%) tested positive for dengue virus. Four out of six dengue viruses from positive samples were successfully isolated. Dengue virus serotype 2 and serotype 3 were found to have circulated in domestic dog populations. One of 153 samples (0.65%) collected from the rubber plantation area showed a PCR-positive result, and dengue serotype 3 was successfully isolated. Partial gene phylogeny revealed that the isolated dengue viruses were closely related to those strains circulating in human populations. None of the 71 samples collected from the island tourist spot showed a positive result.


We concluded that domestic dogs can be infected with dengue virus strains circulating in dengue endemic areas. The role of domestic dogs in dengue transmission needs to be further investigated, i.e., whether they are potential reservoirs or incidental hosts of dengue viruses.

Skeptic Oslerphile, Scientist at the Indian Council of Medical Research, National Institute of Cholera and Enteric Diseases. Interests include: Emerging Infections, Public Health, Antimicrobial Resistance, One Health and Zoonoses, Diarrheal Diseases, Medical Education, Medical History, Open Access, Healthcare Social Media and Health2.0. Opinions are my own!

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