Internal validity of clinical trials for Plasmodium vivax malaria treatment

Resistência parasitária pode ser definida como a habilidade da cepa parasitária de sobreviver e/ou multiplicar, a despeito da administração e absorção da medicação dada em doses iguais ou superiores àquelas usualmente recomendadas, porém dentro do limite de tolerância dos indivíduos. Assim sendo, o desenho de estudo ideal para monitorizar a emergência da resistência parasitária aos antimaláricos deveria utilizar controles históricos ou alguma informação prévia (baseline) válida. Além disso, é fundamental que se tenha algum tipo de controle sobre os demais determinantes de falha terapêutica, não diretamente relacionados ao fenômeno biológico da resistência do parasita, os quais poderiam variar através do tempo e teriam potencial de distorcer a interpretação dos resultados de estudos dessa natureza. No presente artigo são feitas considerações sobre a validade interna de estudos que objetivam avaliar a emergência da resistência in vivo do Plasmodium vivax à doses padronizadas de primaquina usadas rotineiramente pelos serviços de saúde. Poucos foram os estudos que atentaram para a necessidade de controlar os determinantes externos da falha terapêutica, ou que se preocuparam em comparar os resultados encontrados com as taxas de cura historicamente observadas em uma dada região geográfica. Assim, recomenda-se que maior ênfase seja dada à validade interna (e limitações) das conclusões de estudos dessa natureza. _______________________________________________________________________________________ ABSTRACTParasite resistance can be defined as the ability of a parasite strain to survive and/or to multiply despite the administration and absorption of a drug given in doses equal or higher than those usually recommended, but within the limits of tolerance of the patients. Therefore, the ideal study design to be used to monitor emergence of parasite resistance would use historical controls or any valid baseline data. Moreover, it is desirable to have some control of remaining determinants of therapeutic failure, not related to biological parasite resistance, which could vary over time and would have potential to distort the analysis for detecting emergence of parasite resistance. Here we comment on the internal validity of studies, which aim to assess the in vivo Plasmodium vivax emergence of resistance to standard doses of primaquine used routinely by health services. Few studies have paid attention to the need to control for other determinant factors of therapeutic failures or made any attempt to compare current findings with cure failure rates of historical controls from a given geographical area. Therefore, attention to the internal validity (and limitations) of study conclusions in these types of study is strongly advised

The changing distribution of malaria in the Brazilian Amazon, 2003-2004 and 2008-2009

Introduction More than half of the malaria cases reported in the Americas are from the Brazilian Amazon region. While malaria is considered endemic in this region, its geographical distribution is extremely heterogeneous. Therefore, it is important to investigate the distribution of malaria and to determine regions whereby action might be necessary. Methods Changes in malaria indicators in all municipalities of the Brazilian Amazon between 2003-2004 and 2008-2009 were studied. The malaria indicators included the absolute number of malaria cases and deaths, the bi-annual parasite incidence (BPI), BPI ratios and differences, a Lorenz curve and Gini coefficients. Results During the study period, mortality from malaria remained low (0.02% deaths/case), the percent of municipalities that became malaria-free increased from 15.6% to 31.7%, and the Gini coefficient increased from 82% to 87%. In 2003, 10% of the municipalities with the highest BPI accumulated 67% of all malaria cases, compared with 2009, when 10% of the municipalities (with the highest BPI) had 80% of the malaria cases. Conclusions This study described an overall decrease in malaria transmission in the Brazilian Amazon region. As expected, an increased heterogeneity of malaria indicators was found, which reinforces the notion that a single strategy may not bring about uniformly good outcomes. The geographic clustering of municipalities identified as problem areas might help to define better intervention methods

Effects of Upcountry Maui water additives on health.

Since 2001 Upcountry Maui residents have been concerned that water additives may be linked to health problems in their community. A study using phone surveys was conducted to assess this issue. Most people suffered skin rashes, while others experienced eye irritations or respiratory problems. The surveys suggested that these symptoms might have been attributable to the water additives.D35HP16002/PHS HHS/United State

Barriers with Valve Mechanisms Are Predicted to Protect Crops from Slug Carriers of Rat Lungworm Disease

Angiostrongyliasis (Rat Lungworm disease) is an emerging parasitic disease caused by the ingestion of gastropods infected with the neurotropic nematode Angiostrongylus cantonensis. The reduction of crop infestation with infected slug carriers may vary widely by protection method. We explored the application of barriers with valve mechanisms, whereby selective directional forces caused a greater number of slugs to exit than enter the protected plot, leading to decreased slug population densities at a steady state. Using field data, we constructed predictive models to estimate slug population densities at a steady state in protected plots with (1) no valve effect, (2) a valve effect, (3) no valve effect with a single breach of the barrier, (4) a valve effect with a single breach of the barrier, (5) a valve effect with a constant breach of the barrier, and (6) a repelling effect. For all scenarios, plots protected using a barrier with a valve effect had consistently lower slug densities at a steady state. Our findings support the use of barriers with valve mechanisms under different conditions, and potentially in combination with other interventions to reduce the contamination of crops by slug carriers of A. cantonensis. Improving barriers extends beyond disease mitigation to economic and cultural impacts on the local farmer and consumer communities