scholarly journals Personal protection with PBO-pyrethroid synergist-treated nets after 2 years of household use against pyrethroid-resistant Anopheles in Tanzania

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jackline L. Martin ◽  
Franklin W. Mosha ◽  
Eliud Lukole ◽  
Mark Rowland ◽  
Jim Todd ◽  
...  
Keyword(s):  
Pyrethroid Resistance ◽  
Density Ratio ◽  
Household Survey ◽  
Sensu Stricto ◽  
World Health ◽  
Malaria Vectors ◽  
Personal Protection ◽  
North West ◽  
Hole Index ◽  
Health Organization

Abstract Background The spread of pyrethroid resistance in malaria vectors threatens the effectiveness of standard long-lasting insecticidal nets (LLIN). Synergist nets combine pyrethroid (Py) and piperonyl-butoxide (PBO) to enhance potency against resistance mediated by mono-oxygenase mechanisms. Our project assessed personal protection of the World Health Organization first-in-class PBO-Py LLIN (Olyset Plus) versus the standard LLIN (Olyset net) against pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) and An. funestus in North-West Tanzania after 20 months of household use. Methods From a household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected. The physical integrity and hole index (HI) of the nets were assessed, and resting mosquitoes were collected from inside nets and from room walls. The indoor abundance was estimated using CDC light traps and species identified using PCR. The bioefficacy of PBO and standard LLINs against wild Anopheles was assessed using 30-minute cylinder bioassays. Results Of 2397 Anopheles collected, 8.9% (n = 213) were resting inside standard Olyset nets, while none were found inside Olyset Plus nets (PBO-Py LLINs) of any HI category. Resting density of blood-fed mosquitoes was higher on walls of sleeping rooms with Olyset nets compared to Olyset Plus (0.62 vs 0.10, density ratio [DR]: 0.03, 95% CI 0.01–0.13, p < 0.001). Mosquitoes were found inside Olyset nets of all WHO HI categories, but more were collected inside the more damaged nets (HI ≥ 643) than in less damaged (HI 0–64) nets (DR: 6.4, 95% CI 1.1–36.0, p = 0.037). In bioassay, mortality of An. gambiae s.l. was higher with Olyset Plus than with Olyset nets for new nets (76.8% vs 27.5%) and nets used for 20 months (56.8% vs 12.8%); similar trends were observed with An. funestus. Conclusion The PBO-Py LLINs provided improved protection after 20 months of household use, as demonstrated by the higher bioassay mortality and absence of pyrethroid-resistant An. gambiae sensu stricto (s.s.) and An. funestus collected from inside Olyset Plus nets, irrespective of HI category, as compared to Olyset nets.

scholarly journals Personal Protection with PBO-Pyrethroid Synergist Treated Nets After Two Years of Household Use Against Pyrethroid-Resistant Anopheles in Tanzania

2020 ◽  
Author(s):  
Jackline Martin ◽  
Franklin W Mosha ◽  
Eliud Lukole ◽  
Mark Rowland ◽  
Jim Todd ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Pyrethroid Resistance ◽  
Density Ratio ◽  
Household Survey ◽  
Malaria Vectors ◽  
Personal Protection ◽  
Light Traps ◽  
North West ◽  
Hole Index ◽  
Long Lasting Insecticidal Nets

Abstract Background: The spread of pyrethroid resistance in malaria vectors threatens the effectiveness of standard long-lasting insecticidal nets (LLIN). Synergist nets combine pyrethroid (Py) and piperonyl-butoxide (PBO) to enhance potency against resistance mediated by mono-oxygenase mechanisms. Our project assessed personal protection of WHO first-in-class PBO-Py treated nets (Olyset Plus) versus standard LLIN (Olyset net) against pyrethroid resistant Anopheles gambiae and An. funestus in North West Tanzania after 20 months of household use.Methods: From household survey, 39 standard Olyset net and 39 Olyset Plus houses were selected, physical integrity and hole index (HI) of nets assessed, resting mosquitoes collected from inside nets and from room walls, indoor abundance estimated using CDC light traps and species identified using PCR. Residual bio-efficacy of PBO and standard LLINs was assessed using 30 min cylinder bioassays.Results: Of 2397 Anopheles collected, 8.9% (n=213) were resting inside standard Olyset nets while none were found inside Olyset Plus PBO-Py nets of any HI category. Resting density of blood fed mosquitoes was higher on walls of sleeping rooms with Olyset net compared to Olyset Plus (0.62 vs 0.10, density ratio: 0.03, 95% CI: 0.01-0.13, p<0.001). Mosquitoes were found inside Olyset nets of all WHO HI categories but more were collected inside the more damaged (HI≥ 643) nets than in less damaged (HI 0-64) nets (DR: 6.4, 95% CI: 1.1-36.0, p=0.037). In residual bioassay, mortality of An. gambiae s.l was higher with Olyset Plus than with Olyset net for new nets (76.8% vs 27.5%) and 20 months’ nets (56.8% vs 12.8%); similar trends were observed with An. funestus. Conclusion: The PBO-Py treated net provided improved protection after 20 months of household use, as demonstrated by the higher bioassay mortality and absence of pyrethroid resistant An. gambiae s.s. and An. funestus collected from inside Olyset Plus, irrespective of hole index category, as compared to Olyset nets.

scholarly journals Insecticide resistance characteristic of Anopheles vector species successfully controlled by deployment of pyrethroid and PBO long lasting insecticidal treated nets (LLINs) in Tanzania

2021 ◽  
Author(s):  
Johnson Matowo ◽  
David Weetman ◽  
Patricia Pignatell ◽  
Alexandra Wright ◽  
Jacques Charlwood ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Pyrethroid Resistance ◽  
Cluster Randomized Trial ◽  
World Health ◽  
Malaria Vectors ◽  
Metabolizing Enzymes ◽  
Sub Saharan ◽  
Underlying Mechanisms ◽  
Cluster Randomized ◽  
Health Organization

Long lasting insecticidal nets (LLINs) are a proven tool to reduce malaria transmission, but in Africa efficacy is being reduced by pyrethroid resistance in the major vectors. A cluster randomized trial in Muleba district, Tanzania demonstrated that permethrin LLINs co-treated with piperonyl butoxide (PBO), a synergist that can block pyrethroid-metabolizing enzymes in the mosquito, had much greater efficacy than pyrethroid-only nets. Insecticide resistance profiles and underlying mechanisms were investigated in Anopheles gambiae and An. funestus from Muleba during the trial. Diagnostic dose bioassays using permethrin, together with intensity assays, suggest pyrethroid resistance that is both strong and very common, but not extreme. Transcriptomic analysis found multiple P450 genes over expressed including CYP6M2, CYP6Z3, CYP6P3, CYP6P4, CYP6AA1 and CYP9K1 in An. gambiae and CYP6N1, CYP6M7, CYP6M1 and CYP6Z3 in An. funestus. Indeed, very similar suites of P450 enzymes commonly associated with resistant populations elsewhere in Africa were detected as over expressed suggesting a convergence of mechanisms across Sub-Saharan African malaria vectors. The findings give insight into factors that may correlate with pyrethroid PBO LLIN success, broadly supporting model predictions, but revision to guidelines previously issued by the World Health Organization is warranted.

scholarly journals Comparative efficacy of two pyrethroid-piperonyl butoxide nets (Olyset Plus and PermaNet 3.0) against pyrethroid resistant malaria vectors: a non-inferiority assessment

2022 ◽  
Vol 21 (1) ◽  
Author(s):  
Corine Ngufor ◽  
Josias Fagbohoun ◽  
Abel Agbevo ◽  
Hanafy Ismail ◽  
Joseph D. Challenger ◽  
...  
Keyword(s):  
Pyrethroid Resistance ◽  
World Health ◽  
Malaria Vectors ◽  
Comparative Performance ◽  
Mosquito Mortality ◽  
Roof Panel ◽  
Epidemiological Impact ◽  
Health Organization ◽  
Community Trials ◽  
Permanet 3.0

Abstract Background Pyrethroid-PBO nets were conditionally recommended for control of malaria transmitted by mosquitoes with oxidase-based pyrethroid-resistance based on epidemiological evidence of additional protective effect with Olyset Plus compared to a pyrethroid-only net (Olyset Net). Entomological studies can be used to assess the comparative performance of other brands of pyrethroid-PBO ITNs to Olyset Plus. Methods An experimental hut trial was performed in Cové, Benin to compare PermaNet 3.0 (deltamethrin plus PBO on roof panel only) to Olyset Plus (permethrin plus PBO on all panels) against wild pyrethroid-resistant Anopheles gambiae sensu lato (s.l.) following World Health Organization (WHO) guidelines. Both nets were tested unwashed and after 20 standardized washes compared to Olyset Net. Laboratory bioassays were also performed to help explain findings in the experimental huts. Results With unwashed nets, mosquito mortality was higher in huts with PermaNet 3.0 compared to Olyset Plus (41% vs. 28%, P < 0.001). After 20 washes, mortality declined significantly with PermaNet 3.0 (41% unwashed vs. 17% after washing P < 0.001), but not with Olyset Plus (28% unwashed vs. 24% after washing P = 0.433); Olyset Plus induced significantly higher mortality than PermaNet 3.0 and Olyset Net after 20 washes. PermaNet 3.0 showed a higher wash retention of PBO compared to Olyset Plus. A non-inferiority analysis performed with data from unwashed and washed nets together using a margin recommended by the WHO, showed that PermaNet 3.0 was non-inferior to Olyset Plus in terms of mosquito mortality (25% with Olyset Plus vs. 27% with PermaNet 3.0, OR = 1.528, 95%CI = 1.02–2.29) but not in reducing mosquito feeding (25% with Olyset Plus vs. 30% with PermaNet 3.0, OR = 1.192, 95%CI = 0.77–1.84). Both pyrethroid-PBO nets were superior to Olyset Net. Conclusion Olyset Plus outperformed PermaNet 3.0 in terms of its ability to cause greater margins of improved mosquito mortality compared to a standard pyrethroid net, after multiple standardized washes. However, using a margin of non-inferiority defined by the WHO, PermaNet 3.0 was non-inferior to Olyset Plus in inducing mosquito mortality. Considering the low levels of mortality observed and increasing pyrethroid-resistance in West Africa, it is unclear whether either of these nets would demonstrate the same epidemiological impact observed in community trials in East Africa.

scholarly journals Efficacy of interceptor® G2, a long-lasting insecticide mixture net treated with chlorfenapyr and alpha-cypermethrin against Anopheles funestus: experimental hut trials in north-eastern Tanzania

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Patrick K. Tungu ◽  
Elisante Michael ◽  
Wema Sudi ◽  
William W. Kisinza ◽  
Mark Rowland
Keyword(s):  
Pyrethroid Resistance ◽  
Meta Analysis ◽  
Anopheles Funestus ◽  
Blood Feeding ◽  
Significant Loss ◽  
World Health ◽  
Cross Resistance ◽  
Personal Protection ◽  
Experimental Hut ◽  
Field Evidence

Abstract Background The effectiveness of long-lasting insecticidal nets (LLIN), the primary method for preventing malaria in Africa, is compromised by evolution and spread of pyrethroid resistance. Further gains require new insecticides with novel modes of action. Chlorfenapyr is a pyrrole insecticide that disrupts mitochrondrial function and confers no cross-resistance to neurotoxic insecticides. Interceptor® G2 LN (IG2) is an insecticide-mixture LLIN, which combines wash-resistant formulations of chlorfenapyr and the pyrethroid alpha-cypermethrin. The objective was to determine IG2 efficacy under controlled household-like conditions for personal protection and control of wild, pyrethroid-resistant Anopheles funestus mosquitoes. Methods Experimental hut trials tested IG2 efficacy against two positive controls—a chlorfenapyr-treated net and a standard alpha-cypermethrin LLIN, Interceptor LN (IG1)—consistent with World Health Organization (WHO) evaluation guidelines. Mosquito mortality, blood-feeding inhibition, personal protection, repellency and insecticide-induced exiting were recorded after zero and 20 washing cycles. The trial was repeated and analysed using multivariate and meta-analysis. Results In the two trials held in NE Tanzania, An. funestus mortality was 2.27 (risk ratio 95% CI 1.13–4.56) times greater with unwashed Interceptor G2 than with unwashed Interceptor LN (p = 0.012). There was no significant loss in mortality with IG2 between 0 and 20 washes (1.04, 95% CI 0.83–1.30, p = 0.73). Comparison with chlorfenapyr treated net indicated that most mortality was induced by the chlorfenapyr component of IG2 (0.96, CI 0.74–1.23), while comparison with Interceptor LN indicated blood-feeding was inhibited by the pyrethroid component of IG2 (IG2: 0.70, CI 0.44–1.11 vs IG1: 0.61, CI 0.39–0.97). Both insecticide components contributed to exiting from the huts but the contributions were heterogeneous between trials (heterogeneity Q = 36, P = 0.02). WHO susceptibility tests with pyrethroid papers recorded 44% survival in An. funestus. Conclusions The high mortality recorded by IG2 against pyrethroid-resistant An. funestus provides first field evidence of high efficacy against this primary, anthropophilic, malaria vector.

scholarly journals From the Field to the Laboratory: Quantifying Outdoor Mosquito Landing Rate to Better Evaluate Topical Repellents

2021 ◽  
Author(s):  
Mara Moreno-Gómez ◽  
Rubén Bueno-Marí ◽  
Andrea Drago ◽  
Miguel A Miranda
Keyword(s):  
World Health ◽  
Asian Tiger Mosquito ◽  
Personal Protection ◽  
Evaluation Standards ◽  
Testing Conditions ◽  
Vector Borne Diseases ◽  
Asian Tiger ◽  
The World ◽  
Vector Borne ◽  
Health Organization

Abstract Vector-borne diseases are a worldwide threat to human health. Often, no vaccines or treatments exist. Thus, personal protection products play an essential role in limiting transmission. The World Health Organization (WHO) arm-in-cage (AIC) test is the most common method for evaluating the efficacy of topical repellents, but it remains unclear whether AIC testing conditions recreate the mosquito landing rates in the field. This study aimed to estimate the landing rate outdoors, in an area of Europe highly infested with the Asian tiger mosquito (Aedes albopictus (Skuse, 1894, Diptera: Culididae)), and to determine how to replicate this rate in the laboratory. To assess the landing rate in the field, 16 individuals were exposed to mosquitoes in a highly infested region of Italy. These field results were then compared to results obtained in the laboratory: 1) in a 30 m3 room where nine volunteers were exposed to different mosquito abundances (ranges: 15–20, 25–30, and 45–50) and 2) in a 0.064 m3 AIC test cage where 10 individuals exposed their arms to 200 mosquitoes (as per WHO requirements). The highest mosquito landing rate in the field was 26.8 landings/min. In the room test, a similar landing rate was achieved using 15–20 mosquitoes (density: 0.50–0.66 mosquitoes/m3) and an exposure time of 3 min. In the AIC test using 200 mosquitoes (density: 3,125 mosquitoes/m3), the landing rate was 229 ± 48 landings/min. This study provides useful reference values that can be employed to design new evaluation standards for topical repellents that better simulate field conditions.

scholarly journals Survey of hearing disorders in an urban population in Rondonia, Northern Brazil

2013 ◽  
Vol 47 (2) ◽  
pp. 309-315 ◽  
Author(s):  
Maria Cecilia Bevilacqua ◽  
Marcos Roberto Banhara ◽  
Ariadnes Nobrega de Oliveira ◽  
Adriane Lima Mortari Moret ◽  
Katia de Freitas Alvarenga ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Hearing Impairment ◽  
Urban Area ◽  
Pure Tone Audiometry ◽  
Household Survey ◽  
World Health ◽  
Hearing Disorders ◽  
Cross Sectional ◽  
Northern Brazil ◽  
Health Organization

OBJECTIVE: To identify the prevalence of hearing loss for the population in the urban area. METHODS: A cross-sectional household survey based on the World Health Organization Ear and Hearing Disorders Survey Protocol was conducted in 298 households in the urban area of Monte Negro, Rondonia, Northern Brazil, from 2005 to 2007. Ear examinations, behavioral audiometry and pure tone audiometry were conducted on 577 individuals. RESULTS: The results showed that 3.8% (95%CI 2.17;5.45) of population were classified in the disabling hearing impairment category. The prevalence of moderate hearing impairment was 3.4%; severe impairment was 0.4%; and profound hearing impairment was not found. CONCLUSIONS: The impairing hearing loss prevalence found in this study is within of the international prevalence for this level of hearing loss and smaller than observed in a previous study in the South region of Brazil.

Insecticide Resistance in Anopheles stephensi in Somali Region, Eastern Ethiopia

2020 ◽  
Author(s):  
Solomon Yared ◽  
Araya Gebressielasie ◽  
Lambodhar Damodaran ◽  
Victoria Bonnell ◽  
Karen Lopez ◽  
...  
Keyword(s):  
Insecticide Resistance ◽  
Anopheles Stephensi ◽  
Mortality Rates ◽  
Resistance Mechanisms ◽  
World Health ◽  
Malaria Vectors ◽  
Eastern Ethiopia ◽  
Pyrethroid Insecticides ◽  
Pirimiphos Methyl ◽  
Health Organization

Abstract Background: The movement of malaria vectors into new areas is a growing concern in the efforts to control malaria. The recent report of Anopheles stephensi in eastern Ethiopia has raised the necessity to understand the insecticide resistance status of the vector in the region to better inform vector-based interventions. The aim of this study was to evaluate insecticide resistance in An. stephensi in eastern Ethiopia using two approaches: 1) World Health Organization (WHO) bioassay tests in An. stephensi and 2) genetic analysis of insecticide resistance genes in An. stephensi in eastern Ethiopia. Methods: Mosquito larvae and pupae were collected from Kebridehar. Insecticide susceptibility of An. stephensi was tested with malathion 5%, bendiocarb 0.1%, propoxur 0.1%, deltamethrin 0.05%, permethrin 0.75%, Pirimiphos-methyl 0.25% and DDT 4%, according to WHO standard protocols. Results: All An. stephensi samples were resistant to carbamates, with mortality rates 23% and 21% for bendiocarb and propoxur, respectively. Adult An. stephensi was also resistant to pyrethroid insecticides with mortality rates 67% for deltamethrin and 53% for permethrin. Resistance to DDT and malathion was detected in An. stephensi with mortality rates of 32% as well as An. stephensi was resistance to pirimiphos-methyl with mortality rates 14%. Analysis of the voltage gate sodium channel gene (vgsc) revealed the absence of kdr L1014 mutations. Conclusion: Overall, these findings support that An. stephensi is resistant to several classes of insecticides, most notably pyrethroids. However, the absence of the kdr L1014 gene may suggest non-target site resistance mechanisms. Continuous insecticide resistance monitoring should be carried out in the region to confirm the documented resistance and exploring mechanisms conferring resistance in An. stephensi in Ethiopia.

scholarly journals Household Survey of Trachoma Among Children Living in Pernambuco, Brazil

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 263
Author(s):  
Brito ◽  
Barbosa ◽  
Coelho de Andrade ◽  
Sá de Oliveira ◽  
Montarroyos ◽  
...  
Keyword(s):  
Mixed Model ◽  
Family Income ◽  
Univariate Analysis ◽  
Household Survey ◽  
Population Based ◽  
The State ◽  
World Health ◽  
Social Risk ◽  
Piped Water ◽  
Health Organization

This study analyzed the association between individual and household factors and the incidence of trachoma among a population aged between 1 and 9 years in the state of Pernambuco. This was a population-based household study conducted using a population-based sample of residents from 96 census sectors of the 1778 sectors considered to be at social risk in the state. The estimated odds ratio of the univariate analysis presented a confidence interval of 95%. Weights and clusters were adjusted through the Generalized Linear and Latent Mixed Model (GLLAM) method. Trachoma cases were the dependent variable in the multivariate analysis. The independent variables were selected through the stepwise forward method, with an input criterion of 20% (p < 0.20) and an output criterion of 10% (p < 0.10). The prevalence was 6.65%. Trachoma was associated with a female sex, age of 5–9 years, either the absence of use or infrequent use of soap to wash the hands and face, the presence of nasal secretion, a lack of piped water from a public supply system, a greater number of rooms used for sleeping, a greater number of people living in the same household, and a family income of up to one minimum monthly wage. The prevalence of follicular trachoma in Pernambuco was higher than what is recommended by the World Health Organization (WHO).

scholarly journals Evaluating insecticide resistance across African districts to aid malaria control decisions

2020 ◽  
Vol 117 (36) ◽  
pp. 22042-22050 ◽  
Author(s):  
Catherine L. Moyes ◽  
Duncan K. Athinya ◽  
Tara Seethaler ◽  
Katherine E. Battle ◽  
Marianne Sinka ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Pyrethroid Resistance ◽  
Resistance Mechanisms ◽  
World Health ◽  
Malaria Vector Control ◽  
Ensemble Model ◽  
Metabolic Resistance ◽  
The World ◽  
Susceptibility Tests ◽  
Health Organization

Malaria vector control may be compromised by resistance to insecticides in vector populations. Actions to mitigate against resistance rely on surveillance using standard susceptibility tests, but there are large gaps in the monitoring data across Africa. Using a published geostatistical ensemble model, we have generated maps that bridge these gaps and consider the likelihood that resistance exceeds recommended thresholds. Our results show that this model provides more accurate next-year predictions than two simpler approaches. We have used the model to generate district-level maps for the probability that pyrethroid resistance inAnopheles gambiaes.l. exceeds the World Health Organization thresholds for susceptibility and confirmed resistance. In addition, we have mapped the three criteria for the deployment of piperonyl butoxide-treated nets that mitigate against the effects of metabolic resistance to pyrethroids. This includes a critical review of the evidence for presence of cytochrome P450-mediated metabolic resistance mechanisms across Africa. The maps for pyrethroid resistance are available on the IR Mapper website, where they can be viewed alongside the latest survey data.

scholarly journals Catastrophic health expenditure: the case of households with adults over 60 years of age in Peru – 2019

2021 ◽  
Vol 25 (111) ◽  
pp. 191-200
Author(s):  
Mario Villegas Yarleque ◽  
Freddy Carrasco Choque ◽  
Ronald Hidalgo Armestar ◽  
Gretel Fiorella Villegas Aguilar
Keyword(s):  
Health Insurance ◽  
World Health Organization ◽  
Urban Areas ◽  
Health Sector ◽  
Health Spending ◽  
Household Survey ◽  
World Health ◽  
Academic Degree ◽  
Health Organization ◽  
Catastrophic Spending

Within the health sector, it is vitally important to analyze whether households incur catastrophic spending for using such services. In this sense, the study seeks to estimate catastrophic health spending for households with members over 60 years of age. To achieve the objective, the methodology of the World Health Organization was used to find the way in which the household incurs in catastrophic spending, using as an instrument the National Household Survey of Peru, for the year 2019. The main results found were: that families living in urban areas, who have health insurance, who have a higher academic degree, decrease the probability of incurring in catastrophic spending, while being over 60 years old, having a chronic disease, suffering some permanent limitation and not having hygienic services, help to incur in catastrophic spending, so it was concluded that the most vulnerable areas should be attended to achieve a better welfare for older adults. Keywords: catastrophic expense, out-of-pocket expense, health insurance. References [1]J. Alvis, c. Marruco, N. Alvis, F. Gomes, Á. Flores and D. Moreno, «Gasto de bolsillo y gasto catastrófico en salud en los hogares de Cartagena, Colombia,» Salud Publica, 10 2018. [2]E. Giménez, L. Flores, J. Rodriguez, G. Ocampos and N. Peralta, «Gastos catastróficos de salud en los hogares del Paraguay,» Instituto de Investigaciones en Ciencias de la Salud, vol. 16, nº 2, 2018. [3]E. Gonzáles and J. García, «Gastos catastróficos en salud, transferencias gubernamentales y remesas en México, » Papeles de población, vol. 23, nº 91, 2017.[4]A. Hernández, C. Rojas, M. Santero, J. Prado y D.Rosselli, «health-related out-of-pocket expenses in older peruvian adults: analysis of the national householdsurvey on living conditions and poverty 2017,» Rev Peru Med Exp Salud Publica, vol. 35, nº 3, 2017. [5]O. Lazo, J. Alcalde and O. Espinosa, «El sistema de salud en Perú,» Lima , 2016. [6]World Health Organization Geneva, «Distribución del gasto en salud y gastos catastróficos Metodología,» 2005. [7]Organización Mundial de la Salud, «Organización Mundial de la Salud,» 2014. [Online]. Available: https://www.who.int/topics/chronic_diseases/es/. [8]Organización Mundial de la Salud , «Organización Mundial de la Salud,» 2018. [Online]. Available: https://www.who.int/topics/disabilities/es/.  

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