Short Report: Association Between Chloroquine and Amodiaquine Resistance and Allelic Variation in the Plasmodium Falciparum Multiple Drug Resistance 1 Gene and the Chloroquine Resistance Transporter Gene in Isolates from the Upper Nile in Southern Sudan.

Amodiaquine, a 4-aminoquinoline compound, is being considered as an alternative to chloroquine and pyrimethamine/sulfadoxine where resistance in Plasmodium falciparum to both drugs has been selected. Although amodiaquine is more potent than chloroquine, its effectiveness is reduced in areas where chloroquine resistance is high. We report an association of the P. falciparum chloroquine resistance transporter (pfcrt) gene and the P. falciparum multiple drug resistance 1 (pfmdr1) gene, two chloroquine resistance markers, with chloroquine and amodiaquine efficacy in vivo in southern Sudan. The data show that the allele of the pfcrt gene with a lysine to threonine change at codon 76 is strongly associated with both chloroquine and amodiaquine resistance. No such association was observed with the pfmdr1 gene

Drug resistance in Plasmodium falciparum from the Chittagong Hill Tracts, Bangladesh.

OBJECTIVE: To assess the efficacy of antimalarial treatment and molecular markers of Plasmodium falciparum resistance in the Chittagong Hill Tracts of Bangladesh. METHODS: A total of 203 patients infected with P. falciparum were treated with quinine 3 days plus sulphadoxine/pyrimethamine (SP) combination therapy, and followed up during a 4-week period. Blood samples collected before treatment were genotyped for parasite mutations related to chloroquine (pfcrt and pfmdr1 genes) or SP resistance (dhfr and dhps). RESULTS: Of 186 patients who completed follow-up, 32 patients (17.2%) failed to clear parasitaemia or became positive again within 28 days after treatment. Recurring parasitaemia was related to age (chi(2) = 4.8, P < 0.05) and parasite rates on admission (t = 3.1, P < 0.01). PCR analysis showed that some of these cases were novel infections. The adjusted recrudescence rate was 12.9% (95% CI 8.1-17.7) overall, and 16.6% (95% CI 3.5-29.7), 15.5% (95% CI 8.3-22.7) and 6.9% (95% CI 0.4-13.4) in three age groups (<5 years, 5-14, > or =15). The majority of infections carried mutations associated with chloroquine resistance: 94% at pfcrt and 70% at pfmdr. Sp-resistant genotypes were also frequent: 99% and 73% of parasites carried two or more mutations at dhfr and dhps, respectively. The frequency of alleles at dhfr, dhps and pfmdr was similar in cases that were successfully treated and those that recrudesced. CONCLUSIONS: The clinical trial showed that quinine 3-days combined to SP is still relatively effective in the Chittagong Hill Tracts. However, if this regimen is continued to be widely used, further development of SP resistance and reduced quinine sensitivity are to be expected. The genotyping results suggest that neither chloroquine nor SP can be considered a reliable treatment for P. falciparum malaria any longer in this area of Bangladesh

Evaluation of Three Rapid Tests for Diagnosis of P. Falciparum and P. Vivax Malaria in Colombia.

The diagnostic capacity of three malaria rapid diagnostic tests (RDTs), NOW-Malaria-ICT, OptiMAL-IT, and Paracheck-Pf, was evaluated against expert microscopy in Colombia. We tested 896 patients, of whom microscopy confirmed 139 P. falciparum, 279 P. vivax, and 13 mixed P.f/P.v infections and 465 negatives. Paracheck-Pf and NOW-malaria-ICT were more accurate in detecting P. falciparum (sensitivities 90.8% and 90.1%, respectively) in comparison with Optimal-IT (83.6%). NOW showed an acceptable Pf detection rate at low densities (< 500/microL), but resulted in a higher proportion of false positives. For P. vivax diagnosis, Optimal-IT had a higher sensitivity than NOW (91.0% and 81.4%, respectively). The choice between the two Pf/Pv detecting RDTs balances P. falciparum and P. vivax detection rates. Considering some degree of P. falciparum overtreatment and failure to detect all P. vivax cases as more acceptable than missing some cases of P. falciparum, we recommend careful implementation of NOW-malaria-ICT in areas where microscopy is lacking. The price is however still a constraint

Methoderapport om Industriële emissies naar lucht te berekenen (actualisatie 2016) zoals gebruikt door de Emissieregistratie

In this technical report RIVM describes the updated methods that The Netherlands Pollutant Release and Transfer Register uses to calculate the emissions of contaminated substances into the air from the Industry, Energy Generating and Waste Processing sectors. Due to international treaties, such as the Kyoto protocol, the EU Emissions Ceiling (NEC Directive) and the Convention on Long-range Transboundary Air Pollution (CLRTAP), the Netherlands is obliged to always report in accordance with the most recent scientific insights regarding the emission of greenhouse gases, acidifying pollutants and substances related to large-scale air pollution. This description is used to substantiate the reported emissions. This report is targeted at the national and international reviewers that validate Dutch reports to the EU and UN.Het RIVM beschrijft in deze technische rapportage de geactualiseerde methoden waarmee de Nederlandse Emissieregistratie de uitstoot van verontreinigende stoffen naar de lucht berekent vanuit de sectoren Industrie, Energieopwekking en Afvalverwerking. Nederland is vanwege internationale verdragen, zoals het Kyoto-protocol, de EU-Emissieplafonds (NEC-Directive) en de Convention on Long-range Transboundary Air Pollution (CLRTAP), verplicht om steeds volgens de meest actuele wetenschappelijk inzichten te rapporteren over de uitstoot van broeikasgassen, verzurende stoffen en stoffen die gerelateerd zijn aan grootschalige luchtverontreiniging. Met deze beschrijving wordt de gerapporteerde uitstoot onderbouwd. Doelgroep voor deze rapportage zijn de (internationale) reviewers die de Nederlandse rapportages aan de EU en VN valideren.Ministerie van I&

An environmental health guideline for the development of local health policy

GGD'en spelen een belangrijke rol in de advisering van gemeenten bij de ontwikkeling van gemeentelijke nota's lokaal gezondheidsbeleid. Deze nota's beogen een integrale aanpak van gezondheidsbeleid met daarbij zowel aandacht voor het bevorderen van een gezonde leefstijl, als voor het bevorderen van een goede sociale en fysieke omgeving. Deze richtlijn gaat in op het laatstgenoemde onderwerp: milieufactoren en kenmerken van de fysieke omgeving die in relatie staan tot gezondheid. De richtlijn geeft informatie over wet- en regelgeving, over bestuur en bestuurlijke processen en over beleid. Informatie die nuttig is voor het belangrijkste onderdeel van de richtlijn: een stappenplan om beleid op het gebied van milieu en gezondheid te ontwikkelen.Municipal health offices play an important role in the Netherlands in advising local government on the development of local health policy. Policy plans envisage an integral vision on health where attention is paid to both the promotion of a healthy lifestyle and a good social and physical environment. This guideline focuses on the last topic: environmental factors and characteristics of the physical environment in relation to health. It also provides information on legislation and regulation local government and governmental processes and health policy. To sum up, this information that will be useful in building up stepwise guidance for developing environmental health policy.VW

Radiolabeled albumin through S_NAr of cysteines as a potential pretargeting theranostic agent

Human serum albumin (HSA) has been shown to be a promising tumor targeting vector and target for generating theranostics by bioconjugation. Unstable chemical conjugation to HSA via a cysteine (Cys34) by reversible Michael additions is most commonly applied for this purpose. Herein, we describe utilization of our recently developed site-selective irreversible S(N)Ar conjugation to Cys34 using perfluorobenzene sulfonyl derivatives to introduce a trans-cyclooctene (TCO) handle. The TCO could then be bioorthogonally ligated within minutes through an inverse-electron demand Diels–Alder reaction (IEDDA) to tetrazines (Tzs) containing a radionuclide. The methodology opens up a wide range of chemistries including pretargeting, ‘click-to-release’ tumor selective drug delivery or ultra-fast and complete conjugation of any drug. The proof-of-principle study demonstrated that the conjugation chemistry is feasible, robust and easy to carry out, being promising for pretargeted imaging and therapy studies as well as selective drug delivery using HSA

D4.3 : Feedback system description and results report

Report on the description and results of the publicly sign-on accessible feedback system, based on a catalogue integrating the observation inventory