GUARD study report: Good Use of Antimalarials and Rapid Diagnostic Tests in Cambodia study report

Using a mixed methods approach that included quality assessments, a mystery client study and qualitative research, we conducted a comprehensive evaluation of malaria Rapid Diagnostic Tests and in the private sector in 12 health centre catchment areas across Cambodia. In summary, we found that the RDTs collected from drug shops had maintained good quality and that storage and transport conditions were on the whole satisfactory. Uptake of RDTs appeared to highest in the most highly trained providers i.e. “cabinets”, and lowest in grocery shops, with pharmacies and drugs shops having some ambiguity around their role. Findings from the focus group discussions and the mystery client study suggest that some of the problems in uptake and interpretation relate to RDTs being on the margins of practice for these providers who see themselves as either providing a diagnosis and cure (pinit pchier bal) or simply selling drugs for symptomatic relief (lout tnam). Several problems with RDTs were identified in terms of their actual use, in particular relating to interpretation of results, blood safety, and problems related to the buffer and the blood collecting device. In summary this study provides a comprehensive assessment of malaria RDTs in one of the first countries to implement them in the private sector

Assessing the quality of service of village malaria workers to strengthen community-based malaria control in Cambodia

BackgroundMalaria continues to be a major public health problem in remote forested areas in Cambodia. As a national strategy to strengthen community-based malaria control, the Cambodian government has been running the Village Malaria Worker (VMW) project since 2001. This study sought to examine the nature and quality of the VMWs\u27 services.MethodsData collection was carried out in February and March 2008 through interviews with one of the two VMWs who takes the lead in malaria control activities in each of the 315 VMW villages (n = 251). The questionnaire addressed 1) the sociodemographic characteristics of VMWs, 2) service quality, 3) actions for malaria prevention and vector control, and 4) knowledge of malaria epidemiology and vector ecology.ResultsVMWs were effective in conducting diagnosis with Rapid Diagnostic Tests (RDTs) and prescribing anti-malarials to those who had positive RDT results, skills that they had acquired through their training programmes. However, most other services, such as active detection, explanations about compliance, and follow-up of patients, were carried out by only a small proportion of VMWs. The variety of actions that VMWs took for malaria prevention and vector control was small (average action index score 12.8/23), and their knowledge was very limited with less than 20% of the VMWs giving correct answers to six out of seven questions on malaria epidemiology and vector ecology. Knowledge of vector breeding places and malaria transmission were significant determinants of both the quality of VMWs\u27 services and the variety of their actions for malaria prevention and vector control.ConclusionsVMWs\u27 services focused primarily on diagnosis and treatment. Their focus needs to be broadened to cover other aspects of malaria control in order to further strengthen community-based malaria control. VMWs\u27 actions and knowledge also need substantial improvement. Strengthening training programmes can help achieve better performance by VMWs

Allele-Specific Isothermal Amplification Method Using Unmodified Self-Stabilizing Competitive Primers.

Rapid and specific detection of single nucleotide polymorphisms (SNPs) related to drug resistance in infectious diseases is crucial for accurate prognostics, therapeutics and disease management at point-of-care. Here, we present a novel amplification method and provide universal guidelines for the detection of SNPs at isothermal conditions. This method, called USS-sbLAMP, consists of SNP-based loop-mediated isothermal amplification (sbLAMP) primers and unmodified self-stabilizing (USS) competitive primers that robustly delay or prevent unspecific amplification. Both sets of primers are incorporated into the same reaction mixture, but always targeting different alleles; one set specific to the wild type allele and the other to the mutant allele. The mechanism of action relies on thermodynamically favored hybridization of totally complementary primers, enabling allele-specific amplification. We successfully validate our method by detecting SNPs, C580Y and Y493H, in the Plasmodium falciparum kelch 13 gene that are responsible for resistance to artemisinin-based combination therapies currently used globally in the treatment of malaria. USS-sbLAMP primers can efficiently discriminate between SNPs with high sensitivity (limit of detection of 5 × 101 copies per reaction), efficiency, specificity and rapidness (<35 min) with the capability of quantitative measurements for point-of-care diagnosis, treatment guidance, and epidemiological reporting of drug-resistance

Malaria and the mobile and migrant population in Cambodia: a population movement framework to inform strategies for malaria control and elimination.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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

Quality of antimalarials at the epicenter of antimalarial drug resistance: results from an overt and mystery client survey in Cambodia.

Widespread availability of monotherapies and falsified antimalarials is thought to have contributed to the historical development of multidrug-resistant malaria in Cambodia. This study aimed to document the quality of artemisinin-containing antimalarials (ACAs) and to compare two methods of collecting antimalarials from drug outlets: through open surveyors and mystery clients (MCs). Few oral artemisinin-based monotherapies and no suspected falsified medicines were found. All 291 samples contained the stated active pharmaceutical ingredient (API) of which 69% were considered good quality by chemical analysis. Overall, medicine quality did not differ by collection method, although open surveyors were less likely to obtain oral artemisinin-based monotherapies than MCs. The results are an encouraging indication of the positive impact of the country's efforts to tackle falsified antimalarials and artemisinin-based monotherapies. However, poor-quality medicines remain an ongoing challenge that demands sustained political will and investment of human and financial resources

A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria

Artemisinins are the cornerstone of anti-malarial drugs. Emergence and spread of resistance to them raises risk of wiping out recent gains achieved in reducing worldwide malaria burden and threatens future malaria control and elimination on a global level. Genome-wide association studies (GWAS) have revealed parasite genetic loci associated with artemisinin resistance. However, there is no consensus on biochemical targets of artemisinin. Whether and how these targets interact with genes identified by GWAS, remains unknown. Here we provide biochemical and cellular evidence that artemisinins are potent inhibitors of Plasmodium falciparum phosphatidylinositol-3-kinase (PfPI3K), revealing an unexpected mechanism of action. In resistant clinical strains, increased PfPI3K was associated with the C580Y mutation in P. falciparum Kelch13 (PfKelch13), a primary marker of artemisinin resistance. Polyubiquitination of PfPI3K and its binding to PfKelch13 were reduced by the PfKelch13 mutation, which limited proteolysis of PfPI3K and thus increased levels of the kinase, as well as its lipid product phosphatidylinositol-3-phosphate (PI3P). We find PI3P levels to be predictive of artemisinin resistance in both clinical and engineered laboratory parasites as well as across non-isogenic strains. Elevated PI3P induced artemisinin resistance in absence of PfKelch13 mutations, but remained responsive to regulation by PfKelch13. Evidence is presented for PI3P-dependent signalling in which transgenic expression of an additional kinase confers resistance. Together these data present PI3P as the key mediator of artemisinin resistance and the sole PfPI3K as an important target for malaria elimination

History of malaria treatment as a predictor of subsequent subclinical parasitaemia: A cross-sectional survey and malaria case records from three villages in Pailin, western Cambodia

Background: Treatment of the sub-clinical reservoir of malaria, which may maintain transmission, could be an important component of elimination strategies. The reliable detection of asymptomatic infections with low levels of parasitaemia requires high-volume quantitative polymerase chain reaction (uPCR), which is impractical to conduct on a large scale. It is unknown to what extent sub-clinical parasitaemias originate from recent or older clinical episodes. This study explored the association between clinical history of malaria and subsequent sub-clinical parasitaemia. Methods: In June 2013 a cross-sectional survey was conducted in three villages in Pailin, western Cambodia. Demographic and epidemiological data and blood samples were collected. Blood was tested for malaria by high-volume qP

Optimising Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Primaquine, Mass Drug Administration and Artemisinin Resistance

Malaria elimination requires a variety of approaches individually optimized for different transmission settings. A recent field study in an area of low seasonal transmission in South West Cambodia demonstrated dramatic reductions in malaria parasite prevalence following both mass drug administration (MDA) and high treatment coverage of symptomatic patients with artemisinin-piperaquine plus primaquine. This study employed multiple combined strategies and it was unclear what contribution each made to the reductions in malaria.A mathematical model fitted to the trial results was used to assess the effects of the various components of these interventions, design optimal elimination strategies, and explore their interactions with artemisinin resistance, which has recently been discovered in Western Cambodia. The modelling indicated that most of the initial reduction of P. falciparum malaria resulted from MDA with artemisinin-piperaquine. The subsequent continued decline and near elimination resulted mainly from high coverage with artemisinin-piperaquine treatment. Both these strategies were more effective with the addition of primaquine. MDA with artemisinin combination therapy (ACT) increased the proportion of artemisinin resistant infections, although much less than treatment of symptomatic cases with ACT, and this increase was slowed by adding primaquine. Artemisinin resistance reduced the effectiveness of interventions using ACT when the prevalence of resistance was very high. The main results were robust to assumptions about primaquine action, and immunity.The key messages of these modelling results for policy makers were: high coverage with ACT treatment can produce a long-term reduction in malaria whereas the impact of MDA is generally only short-term; primaquine enhances the effect of ACT in eliminating malaria and reduces the increase in proportion of artemisinin resistant infections; parasite prevalence is a better surveillance measure for elimination programmes than numbers of symptomatic cases; combinations of interventions are most effective and sustained efforts are crucial for successful elimination

GENERAL CHARACTERISTICS OF PATIENTS WITH SHOULDER PROBLEMS

Amaç: Omuz ekleminden ve özellikle de eklem çevresindeki yumuşak dokulardan kökenalan problemler üst ekstremite ağrılarının en önemli nedenini oluşturur. Çalışmamızın amacıomuz ağrısı yakınması ile başvuran hastaların klinik özelliklerinin değerlendirilmesidir.Gereç ve yöntem: Omuz ağrısı yakınması ile başvuran 709 hastanın 744 omuzuretrospektif olarak değerlendirildi.Bulgular: Hastaların yaş ortalaması 55,16  10,88 yıl idi ve 395 hastada sağ, 279 hastadasol ve 35 hastada her iki omuz etkilenmişti. Vakaların %35,4'ünde travma öyküsü mevcuttu.Klinik ve radyolojik olarak yapılan değerlendirmelerde hastaların %45'inde subakromiyalsıkışma sendromu, %39,4'ünde rotator kaf rüptürü, %1,5'inde bisipital tendinit, %6,5'indeakromioklavikuler eklem dejenerasyonu, %2,2'sinde kalsifik tendinit, %5'inde donuk omuzve %0,4'ünde glenohumeral eklem artrozu saptandı. Subakromiyal sıkışma sendromu olanhastalar ile rotator kaf rüptürü olan hastaların karşılaştırılmasında rüptürü olan hastalarınyaş ortalamalarının daha yüksek ve "American Shoulder Elbow Score" (ASES) skorlarınındaha düşük olduğu ancak "Constant" skorları arasında herhangi bir fark olmadığı görüldü.Bu iki grup etiolojideki travma açısından değerlendirildiğinde rotator kaf rüptürü olan gruptatravma öyküsünün subakromiyal sıkışma sendromlu hastalara göre anlamlı olarak dahafazla olduğu ve travma öyküsünün rotator kafta rüptür riskini 2,9 kat arttırdığı görüldü.Sonuç: Omuz ağrısı nedenleri arasında rotator kaf sorunları çok önemli bir yer tutmaktadır.Travma ve yaş rotator kafta rüptür insidansını arttırmaktadır.Objective: Problems originating from the shoulder joint and periarticular soft tissues arethe most important causes of upper limb pain. The aim of this study was to investigate theclinical charactersitic patients.Material and method: Seven hundred forty-four shoulders 709 patients wereretrospectively studied.Results: The mean age of the patients was 55.16  10.88 years. Right shoulder wasinvolved in 395 patients, left in 279, and both shoulders in 35 patients. Thirty-five percenthad a history of trauma. According to clinical and radiological assessments, 45 % of patientswere diagnosed as subacromial impingement syndrome, 39.4 % roator cuff tears, 1.5 %bicipital tendinitis, 6.5 % degeneration of the acromioclavicular joint, 2.2 % calcific tendinitis,5 % frozen shoulder, and 0.4 % osteoarthritis of the glenohumeral joint. When the patientswith subacromial impingement syndrome were compared with the patients with rotator cuff tears, the mean age of the patients with rotator cuff tears was significantly higher andAmerican Shoulder Elbow Scores (ASES) were lower than the patients with subacromialimpingement syndrome. There were no significant differences between the Constant scores.Significantly more patients with rotator cuff tears had a history of trauma than patients withsubacromial impingement syndrome, and trauma increased the risk of rotator cuff tears 2.9times.Conclusion: Rotator cuff problems is one of the most common causes of shoulder painand functional limitations. Trauma and age are risk factors for rotator cuff rupture