•Many classes of antibiotic used for humans are also used in food animals, including the highest priority of the critically important antimicrobials for human medicine in the World Health ...Organisation's list.•Penicillins and Tetracyclines classes were the most commonly used antibiotics in many countries.•Improve understanding of the use of antibiotics and factors influencing antibiotic use will help promoting prudent use of antimicrobials in livestock.
This review assesses the evidence for patterns of antibiotic use in pig on the basis of papers published in peer-reviewed journals in English between 2000 and 2017. Thirty-six articles were identified and reviewed, of which more than 85% of studies were conducted in Europe and North America. Penicillins and Tetracyclines groups were the most commonly used antibiotics in many countries. Oral medication in suckling and post-weaning periods were the most common applications of antibiotic administration in pig production. Antibiotic use is driven by age-specific diseases and the common pathogens causing these conditions where epidemiological profiles varied greatly across countries. In addition, the type and size of farm were associated with antibiotic use with finisher and larger farms using more antibiotics than farrow-to-finish and smaller farms. There is variation in the use of the highest priority critically important antimicrobials in humans across studies. However, this review indicates that they are still commonly used in pig production, for treatment and prevention of infection. This evidence calls for global efforts on the prudent use of antibiotics in response to the emergence of antimicrobial resistance (AMR) in the agricultural sector.
Summary Background Primaquine is the only available drug that clears mature Plasmodium falciparum gametocytes in infected human hosts, thereby preventing transmission of malaria to mosquitoes. ...However, concerns about dose-dependent haemolysis in people with glucose-6-phosphate dehydrogenase (G6PD) deficiencies have limited its use. We assessed the dose-response association of single-dose primaquine for gametocyte clearance and for safety in P falciparum malaria. Methods We undertook this randomised, double-blind, placebo-controlled trial with four parallel groups in Jinja district, eastern Uganda. We randomly allocated Ugandan children aged 1–10 years with uncomplicated falciparum malaria and normal G6PD enzyme function to receive artemether–lumefantrine, combined with either placebo or with 0·1 mg/kg, 0·4 mg/kg, or 0·75 mg/kg (WHO reference dose) primaquine base. Randomisation was done with computer-generated four-digit treatment assignment codes allocated to random dose groups in block sizes of 16. Study staff who provided care or assessed outcomes and the participants remained masked to the intervention group after assignment. The primary efficacy endpoint was the non-inferiority of the mean duration of gametocyte carriage in the test doses compared with the reference group of 0·75 mg primaquine per kg, with a non-inferiority margin of 2·5 days. The primary safety endpoint was the superiority of the arithmetic mean maximum decrease in haemoglobin concentration from enrolment to day 28 of follow-up in the primaquine treatment groups compared with placebo, with use of significance testing of pairwise comparisons with a cutoff of p=0·05. The trial is registered with ClinicalTrials.gov , number NCT01365598. Findings We randomly allocated 468 participants to receive artemether–lumefantrine combined with placebo (119 children) or with 0·1 mg/kg (116), 0·4 mg/kg (116), or 0·75 mg/kg (117) primaquine base. The mean duration of gametocyte carriage was 6·6 days (95% CI 5·3–7·8) in the 0·75 mg/kg reference group, 6·3 days (5·1–7·5) in the 0·4 mg/kg primaquine group (p=0·74), 8·0 days (6·6–9·4) in the 0·1 mg/kg primaquine group (p=0·14), and 12·4 days (9·9–15·0) in the placebo group (p<0·0001). No children showed evidence of treatment-related haemolysis, and the mean maximum decrease in haemoglobin concentration was not associated with the dose of primaquine received—it did not differ significantly compared with placebo (10·7 g/L, SD 11·1) in the 0·1 mg/kg (11·4 g/L, 9·4; p=0·61), 0·4 mg/kg (11·3 g/L, 10·0; p=0·67), or 0·75 mg/kg (12·7 g/L, 8·2; p=0·11) primaquine groups. Interpretation We conclude that 0·4 mg/kg primaquine has similar gametocytocidal efficacy to the reference 0·75 mg/kg primaquine dose, but a dose of 0·1 mg/kg was inconclusive for non-inferiority. Our findings call for the prioritisation of further trials into the efficacy and safety of doses of primaquine between 0·1 mg/kg and 0·4 mg/kg (including the dose of 0·25 mg/kg recently recommended by WHO), in view of the potential for widespread use of the drug to block malaria transmission. Funding Wellcome Trust and the Bill & Melinda Gates Foundation.
The relationships between human population movement (HPM) and health are a concern at global level. In the case of malaria, those links are crucial in relation to the spread of drug resistant ...parasites and to the elimination of malaria in the Greater Mekong sub-Region (GMS) and beyond. The mobile and migrant populations (MMP) who are involved in forest related activities are both at high risk of being infected with malaria and at risk of receiving late and sub-standard treatment due to poor access to health services. In Cambodia, in 2012, the National Malaria Control Programme (NMCP) identified, as a key objective, the development of a specific strategy for MMPs in order to address these challenges. A population movement framework (PMF) for malaria was developed and operationalized in order to contribute to this strategy.
A review of the published and unpublished literature was conducted. Based on a synthesis of the results, information was presented and discussed with experienced researchers and programme managers in the Cambodian NMCP and led to the development and refinement of a PMF for malaria. The framework was "tested" for face and content validity with national experts through a workshop approach.
In the literature, HPM has been described using various spatial and temporal dimensions both in the context of the spread of anti-malarial drug resistance, and in the context of malaria elimination and previous classifications have categorized MMPs in Cambodia and the GMS through using a number of different criteria. Building on these previous models, the PMF was developed and then refined and populated with in-depth information relevant to Cambodia collected from social science research and field experiences in Cambodia. The framework comprises of the PMF itself, MMP activity profiles and a Malaria Risk Index which is a summation of three related indices: a vulnerability index, an exposure index and an access index which allow a qualitative ranking of malaria risk in the MMP population. Application of currently available data to the framework illustrates that the highest risk population are those highly mobile populations engaged in forest work.
This paper describes the process of defining MMPs in Cambodia, identifying the different activities and related risks to appropriately target and tailor interventions to the highest risk groups. The framework has been used to develop more targeted behaviour change and outreach interventions for MMPs in Cambodia and its utility and effectiveness will be evaluated as part of those interventions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Decarbonization could lead to benefits for air pollution and child health.•We modelled these impacts in 16 selected global cities.•Removing combustion emissions led to large variations in PM2.5 and ...NO2 reductions.•There were correspondingly large variations in modelled impacts across the cities.•However, there are large uncertainties in some estimates due to data limitations.
Most research on the air pollution-related health effects of decarbonization has focused on adults. We assess the potential health benefits that could be achieved in children and young people in a global sample of 16 cities through global decarbonization actions. We modelled annual average concentrations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at 1x1 km resolution in the cities using a general circulation/atmospheric chemistry model assuming removal of all global combustion-related emissions from land transport, industries, domestic energy use and power generation. We modelled the impact on childhood asthma incidence and adverse birth outcomes (low birthweight, pre-term births) using published exposure–response relationships. Removal of combustion emissions was estimated to decrease annual average PM2.5 by between 2.9 μg/m3 (8.4%) in Freetown and 45.4 μg/m3 (63.7%) in Dhaka. For NO2, the range was from 0.3 ppb (7.9%) in Freetown to 18.8 ppb (92.3%) in Mexico City. Estimated reductions in asthma incidence ranged from close to zero in Freetown, Tamale and Harare to 149 cases per 100,000 population in Los Angeles. For pre-term birth, modelled impacts ranged from a reduction of 135 per 100,000 births in Dar es Salaam to 2,818 per 100,000 births in Bhubaneswar and, for low birthweight, from 75 per 100,000 births in Dar es Salaam to 2,951 per 100,000 births in Dhaka. The large variations chiefly reflect differences in the magnitudes of air pollution reductions and estimated underlying disease rates. Across the 16 cities, the reduction in childhood asthma incidence represents more than one-fifth of the current burden, and an almost 10% reduction in pre-term and low birthweight births. Decarbonization actions that remove combustion-related emissions contributing to ambient PM2.5 and NO2 would likely lead to substantial but geographically-varied reductions in childhood asthma and adverse birth outcomes, though there are uncertainties in causality and the precision of estimates.
Large-scale use of insecticide-treated nets and indoor residual spraying have contributed to a significant decrease in malaria transmission worldwide. Further reduction and progress towards ...elimination, however, require complementary control measures which can address the remaining gaps in protection from mosquito bites. Following the development of novel pyrethroids with high knockdown effects on malaria vectors, programmatic use of spatial repellents has been suggested as one potential strategy to fill the gaps. This report explores social and contextual factors that may influence the relevance, uptake and sustainable use of a spatial repellent in two remote villages in Mondulkiri province, Cambodia, with endemic malaria transmission. The repellent consisted of polyethylene emanators, held in an open plastic frame and impregnated with 10% metofluthrin.
In a baseline survey, 90.9% of households in Ou Chra (n = 30/33) and 96.6% in Pu Cha (n = 57/59) were interviewed. Behavioural data were collected for all household occupants (n = 448). In both villages, there were times and places in which people remained exposed to mosquito bites. Prior to the installation of the repellent, 50.6 and 59.5% of respondents noted that bites occurred "very often" inside the house and in the outdoor area surrounding the house, respectively. Indoor biting was reported to occur more frequently in the evening, followed by at night, while outdoor biting occurred more frequently in the early morning. In a follow-up survey, spatial repellents were well received in both villages, although 63.2% of respondents would not replace bed nets with repellents. Most participants (96.6%) were willing to use the product again; the mean willingness to pay was US$ 0.3 per unit. A preference for local procurement methods emerged.
Widespread use of spatial repellents would not fill all protective gaps, but, if their entomological efficacy can be ascertained, outdoor application has the potential to enhance vector control strategies in Cambodia. Successful implementation would require subsidisation and integration with the existing national malaria control strategy. It is hoped that this study, while contributing to a better understanding of the social contexts of residual malaria transmission, will generate further interest in the evaluation of spatial repellents for malaria control.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
...the participating hospitals were either university hospitals (n = 9) or large teaching hospitals (n = 3), and 11 EDs had paediatric intensive care facilities. Collected data included age, sex, ...season, referral, comorbidity (chronic condition expected to last at least 1 year) 22, triage urgency, fever duration, fever measured at ED, presence of “red traffic light” symptoms for identifying risk of serious illness (alarming signs) (from the National Institute for Health and Care Excellence NICE guideline on fever 23: decreased consciousness, ill appearance, work of breathing, meningeal signs, focal neurology, non-blanching rash, dehydration, status epilepticus), previous antibiotic use, vital signs (heart rate, respiratory rate, oxygen saturation, temperature, capillary refill time), laboratory results (white blood cell count, C-reactive protein CRP, urinalysis), imaging (chest X-ray and other imaging), microbiological investigations (cultures and respiratory viral tests), and disposition (intensive care unit admission, general ward admission or discharge). The focus of infection was categorised as upper respiratory tract (otitis media, tonsillitis/pharyngitis, other), lower respiratory tract, gastrointestinal tract, urinary tract, skin, musculoskeletal, sepsis, central nervous system, flu-like illness, childhood exanthem, inflammatory syndrome, undifferentiated fever, or other. CRP, C-reactive protein; LRTI, lower respiratory tract infection; URTI, upper respiratory tract infection. *Patients could have identified viral co-infection. https://doi.org/10.1371/journal.pmed.1003208.g001 We aimed to improve data quality and standardised data collection by using a training module for the local clinical and research teams to optimise clinical assessment and data collection for febrile children.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cambodia aims to eliminate malaria by 2025, however tackling Plasmodium vivax (P.v) presents multiple challenges. The prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency has prevented ...the deployment of 8-aminoquinolones for "radical cure", due to the risk of severe haemolysis. Patients with P. vivax have therefore continued to experience recurrent relapses leading to cumulative health and socioeconomic burden. The recent advent of point of care testing for G6PD deficiency has made radical cure a possibility, however at the time of the study lack of operational experience and guidance meant that they had not been introduced. This study therefore aimed to design, implement and evaluate a new care pathway for the radical cure of P.vivax. This implementation study took place in Pursat province, Western Cambodia. The interventions were co-developed with key stakeholders at the national, district, and local level, through a continuous process of consultations as well as formal meetings. Mixed methods were used to evaluate the feasibility of the intervention including its uptake (G6PD testing rate and the initiation of primaquine treatment according to G6PD status); adherence (self-reported); and acceptability, using quantitative analysis of primary and secondary data as well as focus group discussions and key informant interviews. The co-development process resulted in the design of a new care pathway with supporting interventions, and a phased approach to their implementation. Patients diagnosed with P.v infection by Village Malaria Workers (VMWs) were referred to local health centres for point-of-care G6PD testing and initiation of radical cure treatment with 14-day or 8-week primaquine regimens depending on G6PD status. VMWs carried out follow-up in the community on days 3, 7 and 14. Supporting interventions included training, community sensitisation, and the development of a smartphone and tablet application to aid referral, follow-up and surveillance. The testing rate was low initially but increased rapidly over time, reflecting the deliberately cautious phased approach to implementation. In total 626 adults received G6PD testing, for a total of 675 episodes. Of these 555 occurred in patients with normal G6PD activity and nearly all (549/555, 98.8%) were initiated on PQ14. Of the 120 with deficient/intermediate G6PD activity 61 (50.8%) were initiated on PQ8W. Self-reported adherence was high (100% and 95.1% respectively). No severe adverse events were reported. The pathway was found to be highly acceptable by both staff and patients. The supporting interventions and gradual introduction were critical to success. Challenges included travel to remote areas and mobility of P.v patients. The new care pathway with supporting interventions was highly feasible with high levels of uptake, adherence and acceptability in this setting where high prevalence of G6PD deficiency is high and there is a well-established network of VMWs. Scaling up of the P.v radical cure programme is currently underway in Cambodia and a decline in reduction in the burden of malaria is being seen, bringing Cambodia a step closer to elimination.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
There is growing interest in the expansion of community health workers programmes in low- and middle-income countries as a cost-effective approach to address shortages of health professionals. ...However, our understanding of the reception of large-scale programmes and how to improve them remains limited, with knowledge gaps about factors that may promote or discourage equitable access to services. This paper examines the case of the Village Malaria Workers (VMW) programme in Cambodia, an extensive community-based intervention for the management of malaria cases in remote rural areas.
Fieldwork was conducted in Kampot province, in six case villages characterised by different programme configuration, population size, and distance to the nearest public health facility. In these locations, in-depth interviews (n = 71) with VMWs, village authorities, and residents were conducted to identify facilitators and challenges to service utilisation. Data analysis was informed by a conceptual framework based on five domains of access to services: awareness, accessibility, accommodation, availability, and acceptability.
Factors that influenced the utilisation of VMW services in our research sites include: the nature of dissemination activities and their ability to reach different population groups; the village topography and the changing road infrastructure; the involvement of VMWs in other community roles and activities; perceptions about the type of disease after the onset of symptoms; the need for comprehensive diagnosis and care; perceptions about the status of VMWs as medical providers; length of VMW appointment.
This study highlights the complexity and diversity of contextual factors that may influence the uptake of a community health programme. As in other countries, continued use of lay health workers in Cambodia to deliver diagnostic and curative services has the potential for great health and economic impact. However, further consideration should be given to the problem of access in different categories of residents and different contexts of implementation. In addition, a comprehensive mapping of changes in disease epidemiology, road infrastructure and the geography of access to services is crucial to inform policy development in this area.
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CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Malaria control activities can have a disproportionately greater impact on Plasmodium falciparum than on P. vivax in areas where both species are coendemic. We investigated temporal trends in ...malaria-related morbidity and mortality in Papua, Indonesia, before and after introduction of a universal, artemisinin-based antimalarial treatment strategy for all Plasmodium species.
A prospective, district-wide malariometric surveillance system was established in April 2004 to record all cases of malaria at community clinics and the regional hospital and maintained until December 2013. In March 2006, antimalarial treatment policy was changed to artemisinin combination therapy for uncomplicated malaria and intravenous artesunate for severe malaria due to any Plasmodium species. Over the study period, a total of 418,238 patients presented to the surveillance facilities with malaria. The proportion of patients with malaria requiring admission to hospital fell from 26.9% (7,745/28,789) in the pre-policy change period (April 2004 to March 2006) to 14.0% (4,786/34,117) in the late transition period (April 2008 to December 2009), a difference of -12.9% (95% confidence interval CI -13.5% to -12.2%). There was a significant fall in the mortality of patients presenting to the hospital with P. falciparum malaria (0.53% 100/18,965 versus 0.32% 57/17,691; difference = -0.21% 95% CI -0.34 to -0.07) but not in patients with P. vivax malaria (0.28% 21/7,545 versus 0.23% 28/12,397; difference = -0.05% 95% CI -0.20 to 0.09). Between the same periods, the overall proportion of malaria due to P. vivax rose from 44.1% (30,444/69,098) to 53.3% (29,934/56,125) in the community clinics and from 32.4% (9,325/28,789) to 44.1% (15,035/34,117) at the hospital. After controlling for population growth and changes in treatment-seeking behaviour, the incidence of P. falciparum malaria fell from 511 to 249 per 1,000 person-years (py) (incidence rate ratio IRR = 0.49 95% CI 0.48-0.49), whereas the incidence of P. vivax malaria fell from 331 to 239 per 1,000 py (IRR = 0.72 95% CI 0.71-0.73). The main limitations of our study were possible confounding from changes in healthcare provision, a growing population, and significant shifts in treatment-seeking behaviour following implementation of a new antimalarial policy.
In this area with high levels of antimalarial drug resistance, adoption of a universal policy of efficacious artemisinin-based therapy for malaria infections due to any Plasmodium species was associated with a significant reduction in total malaria-attributable morbidity and mortality. The burden of P. falciparum malaria was reduced to a greater extent than that of P. vivax malaria. In coendemic regions, the timely elimination of malaria will require that safe and effective radical cure of both the blood and liver stages of the parasite is widely available for all patients at risk of malaria.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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