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1.
Clin Exp Dermatol ; 46(7): 1181-1188, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33811771

RESUMO

The ectoparasite Pthirus pubis (PtP), commonly known as the crab or pubic louse, has plagued primates from prehistoric apes to Homo sapiens. We combed the literature from antiquity to the present day, reviewing the pubic louse's origins, its evolution with mankind, and its presentation and management. MEDLINE and EMBASE provided the greatest yield of literature compared with other databases. Estimates for PtP incidence range from 0.3% to 4.6% and for prevalence around 2% in adults. War, disasters and overcrowding support lice transmission, but modern pubic hair grooming has reduced the incidence of PtP in recent years. PtP, is usually found on pubic hair, but may infest scalp and body hair, eyebrows and eyelashes. Reports suggest the possibility of PtP as a vector for Bartonella spp. and Acinetobacter spp., which require further study. Transmission of PtP is via close contact, so sexual abuse and concomitant sexually transmitted infections should be considered. Symptoms and signs of infestation include pruritus, red papules and rust/brown deposits from feeding or faecal matter. Visualization of live lice confirms the diagnosis. Traditional treatments include hand-picking and combing, but in modern times pediculicidal products may generate faster resolution. Permethrin or pyrethrins are the first-line recommendations. Resistance to pediculicides is common with head lice and is presumed likely with PtP, although data are lacking. Pseudoresistance occurs as a result of poor compliance, incorrect or ineffective dosing, and reinfestation. In true resistance, a different pediculicide class should be used, e.g. second-line agents such as phenothrin, malathion or ivermectin. Lice have existed long before humans and given their adaptability, despite habitat challenges from fashion trends in body hair removal, are likely to continue to survive.


Assuntos
Inseticidas/uso terapêutico , Infestações por Piolhos , Phthirus , Animais , História do Século XVI , História do Século XX , História Antiga , Humanos , Resistência a Inseticidas , Inseticidas/história , Ivermectina/uso terapêutico , Infestações por Piolhos/tratamento farmacológico , Infestações por Piolhos/epidemiologia , Infestações por Piolhos/história , Infestações por Piolhos/terapia , Permetrina/uso terapêutico , Piretrinas/uso terapêutico
2.
Angew Chem Int Ed Engl ; 56(34): 10026-10032, 2017 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-28608639

RESUMO

Fake news?? The contact insecticide DDT has been reappraised as a safe, life-saving compound by special interest groups committed to repealing environmental regulations. It is shown in this essay how some specific toxicological data has been misused by those aiming to disingenuously influence public policy. Graphic: Pestroy, a DDT-laced coating marketed in 1946 by Sherwin-Williams Research Laboratories.


Assuntos
Conservação dos Recursos Naturais , DDT/toxicidade , Política Ambiental , Inseticidas/toxicidade , Animais , Conservação dos Recursos Naturais/história , Conservação dos Recursos Naturais/legislação & jurisprudência , DDT/síntese química , DDT/química , DDT/história , Política Ambiental/história , Política Ambiental/legislação & jurisprudência , História do Século XIX , História do Século XX , Inseticidas/síntese química , Inseticidas/química , Inseticidas/história
3.
An. R. Acad. Farm ; 83(2): 167-174, abr.-jun. 2017. ilus
Artigo em Espanhol | IBECS | ID: ibc-164595

RESUMO

Hoy, muchas enfermedades son tratadas gracias al descubrimiento de compuestos a partir de las plantas, lo que evidencia que estas juegan un papel significativo en el descubrimiento y desarrollo de nuevos fármacos. Una de las alternativas para el control de la morbi-mortalidad por malaria es la quimioterapia, la cual ha sido posible gracias al descubrimiento de compuestos a partir de las plantas. En la actualidad, cerca de la mitad de los fármacos antimaláricos disponibles son compuestos naturales o están relacionados con ellos. En esta revisión se hace un recuento histórico del origen y desarrollo de los principales antimaláricos como instrumento de hechos arquitectónicos, que mantienen una estrecha relación con los referentes antimaláricos, que sirven de modelos para profundizar en la búsqueda de nuevas sustancias químicas naturales que podrían contribuir al control de una devastadora enfermedad como la malaria, donde se están presentando cepas resistentes de Plasmodium a los principales tratamientos, falla terapéutica, además de un escaso acceso a los medicamentos, entre otros factores; que complican su prevención y tratamiento (AU)


Today, many diseases are treated thanks to the discovery of compounds from plants, which shows that they play a significant role in the discovery and development of new drugs. One of the alternatives for the control of malaria morbidity and mortality is chemotherapy, which has been made possible by the discovery of compounds from plants. At present, about half of the available antimalarials drugs are naturally occurring compounds or are related to them. This review provides a historical account of the origin and development of the main antimalarials as an instrument of architectural facts, which maintains a close relationship with the antimalarials referents, which serve as models to deepen the search for new natural chemical substances that could contribute to the Control of a devastating disease like malaria, where resistant strains of Plasmodium are being presented to the main treatments, therapeutic failure, in addition to poor access to medicines, among other factors; which complicate their prevention and treatment (AU)


Assuntos
Humanos , Antimaláricos/história , Malária/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Plasmodium/patogenicidade , DDT/história , Inseticidas/história , Erradicação de Doenças/tendências , Quinina/uso terapêutico , Artemisininas/história
4.
Bioorg Med Chem ; 24(3): 317-41, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26725441

RESUMO

In this review, the synthesis of 30 agrochemicals that received an international standardization organization (ISO) name during the last five years (January 2010 to December 2014) is described. The aim is to showcase the range and scope of chemistries used to discover or produce the latest active ingredients addressing the crop protection industry's needs.


Assuntos
Agroquímicos/síntese química , Antinematódeos/síntese química , Fungicidas Industriais/síntese química , Herbicidas/síntese química , Inseticidas/síntese química , Agroquímicos/história , Agroquímicos/normas , Antinematódeos/história , Antinematódeos/normas , Fungicidas Industriais/história , Fungicidas Industriais/normas , Herbicidas/história , Herbicidas/normas , História do Século XXI , Humanos , Inseticidas/história , Inseticidas/normas
5.
Pest Manag Sci ; 71(6): 801-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25124081

RESUMO

The discovery of resmethrin almost five decades ago was the seminal event in the development of pyrethroid insecticides as important pest management tools, the value of which endures to this day. This brief review considers the development of pyrethroids from the perspective of the discovery of resmethrin. I describe the pathway to the discovery of resmethrin and the unique properties that differentiated it from the pyrethrins and earlier synthetic pyrethroids is described. I also summarize information on metabolic fate and mechanisms of selective toxicity, first elucidated with resmethrin, that have shaped our understanding of pyrethroid toxicology since that time. Finally, I review the discovery pathway that led from resmethrin to the development of the first photostable, agriculturally useful pyrethroids that established the importance of this insecticide class.


Assuntos
Piretrinas/farmacologia , Animais , História do Século XX , História do Século XXI , Inseticidas/química , Inseticidas/história , Inseticidas/farmacologia , Dose Letal Mediana , Piretrinas/química , Piretrinas/história
6.
Chem Biol Interact ; 203(1): 221-5, 2013 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-22926007

RESUMO

The anticholinesterase (antiChE) organophosphorus (OP) and methylcarbamate (MC) insecticides have been used very effectively as contact and systemic plant protectants for seven decades. About 90 of these compounds are still in use - the largest number for any insecticide chemotype or mode of action. In both insects and mammals, AChE inhibition and acetylcholine accumulation leads to excitation and death. The cholinergic system of insects is located centrally (where it is protected from ionized OPs and MCs) but not at the neuromuscular junction. Structural differences between insect and mammalian AChE are also evident in their genomics, amino acid sequences and active site conformations. Species selectivity is determined in part by inhibitor and target site specificity. Pest population selection with OPs and MCs has resulted in a multitude of modified AChEs of altered inhibitor specificity some conferring insecticide resistance and others enhancing sensitivity. Much of the success of antiChE insecticides results from a suitable balance of bioactivation and detoxification by families of CYP450 oxidases, hydrolases, glutathione S-transferases and others. Known inhibitors for these enzymes block detoxification and enhance potency which is particularly important in resistant strains. The current market for OPs and MCs of 19% of worldwide insecticide sales is only half of that of 10 years ago for several reasons: there have been no major new compounds for 30 years; resistance has eroded their effectiveness; human toxicity problems are still encountered; the patents have expired reducing the incentive to update registration packages; alternative chemotypes or control methods have been developed. Despite this decline, they still play a major role in pest control and the increasing knowledge on their target sites and metabolism may make it possible to redesign the inhibitors for insensitive AChEs and to target new sites in the cholinergic system. The OPs and MCs are down but not out.


Assuntos
Inibidores da Colinesterase , Inseticidas , Acetilcolinesterase/química , Acetilcolinesterase/genética , Acetilcolinesterase/metabolismo , Animais , Carbamatos/história , Carbamatos/metabolismo , Carbamatos/farmacologia , Domínio Catalítico , Inibidores da Colinesterase/história , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Resistência a Medicamentos , História do Século XX , História do Século XXI , Humanos , Insetos/efeitos dos fármacos , Insetos/metabolismo , Inseticidas/história , Inseticidas/metabolismo , Inseticidas/farmacologia , Modelos Moleculares , Compostos Organofosforados/história , Compostos Organofosforados/metabolismo , Compostos Organofosforados/farmacologia , Filogenia
7.
Pestic Biochem Physiol ; 107(1): 8-17, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25149229

RESUMO

There is an on-going need for the discovery and development of new insecticides due to the loss of existing products through the development of resistance, the desire for products with more favorable environmental and toxicological profiles, shifting pest spectrums, and changing agricultural practices. Since 1960, the number of research-based companies in the US and Europe involved in the discovery of new insecticidal chemistries has been declining. In part this is a reflection of the increasing costs of the discovery and development of new pesticides. Likewise, the number of compounds that need to be screened for every product developed has, until recently, been climbing. In the past two decades the agrochemical industry has been able to develop a range of new products that have more favorable mammalian vs. insect selectivity. This review provides an analysis of the time required for the discovery, or more correctly the building process, for a wide range of insecticides developed during the last 60 years. An examination of the data around the time requirements for the discovery of products based on external patents, prior internal products, or entirely new chemistry provides some unexpected observations. In light of the increasing costs of discovery and development, coupled with fewer companies willing or able to make the investment, insecticide resistance management takes on greater importance as a means to preserve existing and new insecticides.


Assuntos
Inseticidas , Indústria Química/economia , Indústria Química/história , Custos e Análise de Custo , História do Século XX , História do Século XXI , Resistência a Inseticidas , Inseticidas/economia , Inseticidas/história , Pesquisa/economia , Pesquisa/história
8.
Ambix ; 59(2): 88-108, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23057183

RESUMO

The use of chemical pesticides increased considerably after World War II, and ecological damage was noticeable by the late 1940s. This paper outlines some ecological problems experienced during the post-war period in the UK, and in parts of what is now Malaysia. Also discussed is the government's response. Although Rachel Carson's book, Silent Spring (1962), was important in bringing the problems to a wider public, she was not alone in sounding the alarm. Pressure from the public and from British scientists led, among other things, to the founding of the Natural Environment Research Council in 1965. By the 1970s, environmentalism was an important movement, and funding for ecological and environmental research was forthcoming even during the economic recession. Some of the recipients were ecologists working at Imperial College London. Moved by the political climate, and by the evidence of ecological damage, they carried out research on the biological control of insect pests.


Assuntos
Meio Ambiente , Inseticidas/história , Controle Biológico de Vetores/história , Controle de Pragas/história , Agricultura/história , Agricultura/instrumentação , Agricultura/métodos , História do Século XX , Inseticidas/toxicidade , Malásia , Controle de Pragas/métodos , Controle de Pragas/normas , Controle Biológico de Vetores/métodos , Controle Biológico de Vetores/normas , Reino Unido
9.
Environ Health Perspect ; 120(4): 487-93, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22472325

RESUMO

BACKGROUND: Pesticide-environment interactions are bidirectional. The environment alters pesticides by metabolism and photodegradation, and pesticides in turn change the environment through nontarget or secondary effects. OBJECTIVES: Approximately 900 currently used commercial pesticides of widely diverse structures act by nearly a hundred mechanisms to control insects, weeds, and fungi, usually with minimal disruption of nature's equilibrium. Here I consider some aspects of the discovery, development, and use of ecofriendly or green pesticides (i.e., pesticides that are safe, effective, and biodegradable with minimal adverse secondary effects on the environment). Emphasis is given to research in my laboratory. DISCUSSION: The need for understanding and improving pesticide-environment interactions began with production of the first major insecticide approximately 150 years ago: The arsenical poison Paris Green was green in color but definitely not ecofriendly. Development and use of other pesticides has led to a variety of problems. Topics considered here include the need for high purity [e.g., hexachlorocyclohexane and polychloroborane isomers and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)], environmental degradation and the bioactivity of resulting photoproducts and metabolites, pesticide photochemistry (including the use of structural optimization, photostabilizers, and photosensitizers to achieve suitable persistence), the presence of multiple active ingredients in botanical insecticides, the need to consider compounds with common mechanisms of action, issues related to primary and secondary targets, and chemically induced or genetically modified changes in plant biochemistry. Many insecticides are bird, fish, and honeybee toxicants, whereas herbicides and fungicides pose fewer environmental problems. CONCLUSION: Six factors have contributed to the greening of pesticide-environment interactions: advances in pesticide chemistry and toxicology, banning of many chlorinated hydrocarbons, the development of new biochemical targets, increased reliance on genetically modified crops that reduce the amount and variety of pesticides applied, emphasis on biodegradability and environmental protection, and integrated pest- and pesticide-management systems.


Assuntos
Meio Ambiente , Praguicidas/história , Praguicidas/farmacologia , Animais , Ecotoxicologia , Política Ambiental , Fungos/efeitos dos fármacos , Fungicidas Industriais/química , Fungicidas Industriais/história , Fungicidas Industriais/farmacologia , Fungicidas Industriais/toxicidade , Regulamentação Governamental , Herbicidas/química , Herbicidas/história , Herbicidas/farmacologia , Herbicidas/toxicidade , História do Século XX , História do Século XXI , Insetos/efeitos dos fármacos , Inseticidas/química , Inseticidas/história , Inseticidas/farmacologia , Inseticidas/toxicidade , Praguicidas/química , Praguicidas/toxicidade , Plantas/efeitos dos fármacos , Plantas Geneticamente Modificadas , Especificidade da Espécie , Vertebrados/metabolismo
10.
J Hist Med Allied Sci ; 66(3): 347-76, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20624820

RESUMO

In 1945, a United States Public Health Service team in Monrovia, Liberia, began the use of synthetic insecticides for indoor residual spraying (IRS) and as a larvicide, with the goal of controlling malaria in the Liberian capital. In the early 1950s, the project was "scaled up" to reach the surrounding areas, and in 1953, the World Health Organization (WHO) launched an antimalaria program in the upcountry region of Central Province, Liberia. It was initially based solely upon IRS, as it was one of a series of pilot projects whose goal was to determine the feasibility of malaria eradication in tropical Africa. The malaria control project in Monrovia constituted the first large-scale use of synthetic insecticide to combat malaria in tropical Africa, and the WHO pilot project in Central Province was one of a first cluster of projects initiated to explore the efficacy of IRS in a variety of African ecological zones. These projects encountered a spate of difficulties that foreshadowed the general retreat from malaria eradication efforts across tropical Africa by the mid-1960s.


Assuntos
DDT/história , Inseticidas/história , Malária/história , Controle de Mosquitos/história , Medicina Tropical/história , África , História do Século XX , Humanos , Líbia , Malária/prevenção & controle , Estados Unidos , United States Public Health Service , Organização Mundial da Saúde
11.
Pest Manag Sci ; 66(11): 1163-70, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20552666

RESUMO

The crowning achievement for Michael Elliott came in 1973 when his most outstanding candidate insecticide from 25 years of research crystallized from hexane solution. The stereochemically pure crystalline compound was the most potent synthetic insecticide ever made until that time, and it was highly selective for insects compared with mammals. It was given the name deltamethrin. Sequential stereospecific crystallization to isolate the most potent epimer and base-catalyzed racemization of the remaining less active isomer could be used to produce deltamethrin efficiently on a large scale; it became the billion dollar crystals. Elliott's discoveries at Rothamsted in England with Norman Janes and David Pulman of resmethrin, permethrin, cypermethrin and ultimately deltamethrin provided crop protection and malaria control for millions of people. Michael also laid the background for lipophilic amide, dithiane and other insecticides and nerve probes that are not involved in pyrethroid cross-resistance. Some aspects of these investigations were best conducted at Berkeley, where Michael studied pyrethrins in 1969, synthetic pyrethroids in 1974 and alternative insecticides in 1986-1988. This review considers Michael's seminal discoveries in insecticide chemistry, with emphasis on his Berkeley years.


Assuntos
Controle de Insetos/história , Inseticidas/história , Amidas/síntese química , Amidas/química , Amidas/história , Animais , Chrysanthemum cinerariifolium/química , História do Século XX , Insetos , Inseticidas/química , Piretrinas/síntese química , Piretrinas/química , Piretrinas/história , Quinolizinas/síntese química , Quinolizinas/química , Quinolizinas/história , Compostos de Enxofre/síntese química , Compostos de Enxofre/química , Compostos de Enxofre/história
15.
Nihon Ishigaku Zasshi ; 55(1): 15-30, 2009 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-19831251

RESUMO

Immediately after World War II, malaria became one of the major infectious disease threats in Japan. The prevalence of malaria was high in all regions in the summer of 1946. In most prefectures, the prevalence decreased with time thereafter and virtually no epidemics occurred after 1947. Shiga Prefecture, however, was an exception to this pattern. The epidemics in the prefecture occurred repeatedly until 1949, and the prevalence rapidly decreased in 1950. While the epidemics in most prefectures were caused by "imported malaria," those in Shiga Prefecture were caused by "indigenous malaria." This paper focuses on the eradication campaign of "endemic" malaria in Hikone City, Shiga prefecture after WWII. The city government began the campaign in April 1949. They established a malaria research institute for developing and implementing plans. The widespread spraying of insecticides such as DDT was implemented throughout the city and the moat around Hikone Castle was filled in, in order to reduce the mosquito population. Residents also cooperated extensively with programs for sanitation and health education. As a result of these efforts, malaria was completely eliminated in the city within six years. Malaria is still a life-threatening illness for many people in tropical areas of the world. Hikone's postwar experience could provide important lessons for malaria control programs in many places.


Assuntos
Doenças Endêmicas/história , Malária/história , Controle de Mosquitos/história , Saúde Pública/história , Academias e Institutos/história , DDT/história , Surtos de Doenças/história , Surtos de Doenças/prevenção & controle , Doenças Endêmicas/prevenção & controle , Educação em Saúde/história , História do Século XX , Humanos , Inseticidas/história , Japão/epidemiologia , Malária/epidemiologia , Malária/prevenção & controle , Prevalência , Saneamento/história
16.
Pest Manag Sci ; 65(12): 1267-86, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19834884

RESUMO

Fifty years ago, Stern, Smith, van den Bosch and Hagen outlined a simple but sophisticated idea of pest control predicated on the complementary action of chemical and biological control. This integrated control concept has since been a driving force and conceptual foundation for all integrated pest management (IPM) programs. The four basic elements include thresholds for determining the need for control, sampling to determine critical densities, understanding and conserving the biological control capacity in the system and the use of selective insecticides or selective application methods, when needed, to augment biological control. Here we detail the development, evolution, validation and implementation of an integrated control (IC) program for whitefly, Bemisia tabaci (Genn.), in the Arizona cotton system that provides a rare example of the vision of Stern and his colleagues. Economic thresholds derived from research-based economic injury levels were developed and integrated with rapid and accurate sampling plans into validated decision tools widely adopted by consultants and growers. Extensive research that measured the interplay among pest population dynamics, biological control by indigenous natural enemies and selective insecticides using community ordination methods, predator:prey ratios, predator exclusion and demography validated the critical complementary roles played by chemical and biological control. The term 'bioresidual' was coined to describe the extended environmental resistance from biological control and other forces possible when selective insecticides are deployed. The tangible benefits have been a 70% reduction in foliar insecticides, a >$200 million saving in control costs and yield, along with enhanced utilization of ecosystem services over the last 14 years.


Assuntos
Hemípteros , Controle de Pragas/história , Controle de Pragas/métodos , Animais , Arizona , Ecossistema , Hemípteros/efeitos dos fármacos , Hemípteros/fisiologia , História do Século XX , Inseticidas/economia , Inseticidas/história , Inseticidas/farmacologia , Modelos Biológicos , Controle de Pragas/economia , Controle Biológico de Vetores/história , Dinâmica Populacional
17.
Pest Manag Sci ; 65(12): 1311-20, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19842090

RESUMO

In the 'Integrated Control Concept', Stern et al. emphasized that, although insecticides are necessary for agricultural production, they should only be used as a last resort and as a complement to biological control. They argued that selective insecticide use should only be attempted after it has been determined that insect control with naturally occurring biotic agents is not capable of preventing economic damage. However, they concluded their seminal paper by emphasizing that integrated control will not work where natural enemies are inadequate or where economic thresholds are too low to rely on biological control. Thus, it is no surprise that insect control in high-value, fresh-market lettuce crops grown in the desert southwest have relied almost exclusively on insecticides to control a complex of mobile, polyphagous pests. Because lettuce and leafy greens are short-season annual crops with little or no tolerance for insect damage or contamination, biological control is generally considered unacceptable. High expectations from consumers for aesthetically appealing produce free of pesticide residues further forces vegetable growers to use chemical control tactics that are not only effective but safe. Consequently, scientists have been developing integrated pest management (IPM) programs for lettuce that are aimed at reducing the economic, occupational and dietary risks associated with chemical controls of the past. Most of these programs have drawn upon the integrated control concept and promote the importance of understanding the agroecosystem, and the need to sample for pest status and use action thresholds for cost-effective insect control. More recently, pest management programs have implemented newly developed, reduced-risk chemistries that are selectively efficacious against key pests. This paper discusses the influence that the integrated control concept, relative to zero-tolerance market standards and other constraints, has had on the adoption of pest management in desert lettuce crops.


Assuntos
Controle de Insetos/história , Insetos/efeitos dos fármacos , Inseticidas/farmacologia , Lactuca/parasitologia , Doenças das Plantas/parasitologia , Animais , Qualidade de Produtos para o Consumidor , Clima Desértico , História do Século XX , Humanos , Controle de Insetos/economia , Insetos/fisiologia , Inseticidas/história , Controle Biológico de Vetores , Sudoeste dos Estados Unidos
18.
Mt Sinai J Med ; 76(5): 468-73, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19787648

RESUMO

Malaria, a serious disease for all of human history, was not effectively handled until methods for control of its insect vector, the Anopheles mosquito, were developed at the beginning of the 20th century. The Rockefeller Foundation's antimalaria program spread vector-control strategies throughout the world, and its adoption of dichlorodiphenyltrichloroethane during World War II created an especially powerful and effective malaria control strategy. However, insect resistance to dichlorodiphenyltrichloroethane and restrictions on dichlorodiphenyltrichloroethane use due to its long-term environmental effects are factors in the persistence of malaria as a serious health problem. Mt Sinai J Med 76:468-473, 2009. (c) 2009 Mount Sinai School of Medicine.


Assuntos
Antimaláricos/história , Fundações/história , Malária/história , Animais , Antimaláricos/uso terapêutico , Diclorodifenildicloroetano/história , Saúde Global , História do Século XX , Humanos , Inseticidas/história , Malária/prevenção & controle , Estados Unidos , Zoonoses/história
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