Top PDF Tick-borne ehrlichiosis infection in human beings

Tick-borne ehrlichiosis infection in human beings

Tick-borne ehrlichiosis infection in human beings

Human monocytic ehrlichiosis is a tick-borne infectious disease transmitted by several tick species, especially Amblyomma spp caused by Ehrlichia chaffeensis. E. chaffeensis is an obligatory intracel- lular, tick-transmitted bacterium that is maintained in nature in a cycle involving at least one and per- haps several vertebrate reservoir hosts. Two additional Ehrlichia spp, Anaplasma (formerly Ehrlichia) phagocytophila (the agent of human granulocytic ehrlichiosis [HGE]) and E. ewingii (a cause of granu- locytic ehrlichiosis in dogs) act as human pathogens. Human E. chaffeensis infections have generally been reported in North America, Asia and Europe, but recently human cases have been reported in Brazil only. Human monocytic ehrlichiosis is diagnosed by demonstration of a four-fold or greater change in antibody titer to E. chaffeensis antigen by IFA in paired serum samples, or a positive PCR assay and confirmation of E. chaffeensis DNA, or identification of morulae in leukocytes and a posi- tive IFA titer to E. chaffeensis antigen, or immunostaining of E. chaffeensis antigen in a biopsy or autopsy sample, or culture of E. chaffeensis from a clinical specimen.
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Universidade Nova de Lisboa Instituto de Higiene e Medicina Tropical Differential expression and functional characterization of cattle tick genes in response to pathogen infection (Babesia

Universidade Nova de Lisboa Instituto de Higiene e Medicina Tropical Differential expression and functional characterization of cattle tick genes in response to pathogen infection (Babesia

The “One Health” approach recognizes the need for veterinarians, human health professionals, and environmental scientists to work together given the dynamic interface among people, animals, and the environment. This approach is increasingly important for zoonotic diseases, such as TBDs, which rely on animals as reservoirs. As ecological niches flux, opportunities arise for vectors to interact with novel species, allowing infectious agents to broaden both geographic and host ranges. Habitat change has been linked to the emergence of novel human and veterinary disease agents, and can dramatically facilitate expansion opportunities by allowing existing vector populations to flourish and by supporting the establishment of new pathogen maintenance systems (Little, 2013). Ticks are of great medical and veterinary importance as they can transmit a wide variety of infectious agents to different vertebrate hosts (de la Fuente et al., 2008a). In particular bovine babesiosis transmitted by cattle ticks continues having a great economic impact in cattle industry due to the lack of effective control methods (both tick control and disease control). With the premise that improved (e.g. multi-antigen) vaccine formulations and the discovery of new tick-protective antigens related to infection will improve control of tick and tick-borne diseases as well as increase our understanding on tick-pathogen interface, this PhD project was designed with three main objectives:
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Endemic foci of the tick-borne relapsing fever spirochete Borrelia crocidurae in Mali, West Africa, and the potential for human infection.

Endemic foci of the tick-borne relapsing fever spirochete Borrelia crocidurae in Mali, West Africa, and the potential for human infection.

Our MLST method identified the spirochete isolates as B. crocidurae and identified four distinct genomic groups. We and other collaborators have used this approach to characterize the North American relapsing fever spirochetes B. hermsii, B. turicatae and B. parkeri [49,76,77]. Toledo and colleagues applied MLST to identify an isolate of relapsing fever spirochete from Spain as Borrelia hispanica [65]. Recently, the chromosomes of B. recurrentis A1, B. duttonii Ly and B. crocidurae Achema were aligned to identify homologous non-coding, intergenic spacer sequences (not the IGS locus) that were used to develop a PCR – DNA sequence typing scheme to distinguish these three species of spirochetes [53]. This multispacer sequence typing utilized the concatenated sequence of five intergenic spacers that totaled approximately 2,300 bp. The method was applied to 60 samples of infected human blood from relapsing fever patients from Ethiopia (30 B. recurrentis samples), Tanzania (17 B. duttonii samples) and Senegal (13 B. crocidurae samples). The method clearly distinguished the three species of spirochetes with no overlap, which was not the case when using the IGS region [78,79]. The method also demonstrated seven types among the 13 samples of B. crocidurae compared to only five types among the 47 samples representing the other two species [53]. Clearly, a pattern is emerging from our efforts and those of Elbir and colleagues [53] that shows a much more diverse population structure for B. crocidurae, an enzootic pathogen with multiple vertebrate hosts, than has yet been demonstrated for either B. recurrentis or B. duttonii, neither of which has a nonhuman vertebrate host.
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MOLECULAR INVESTIGATION OF HEMOTROPIC MYCOPLASMAS IN HUMAN BEINGS, DOGS AND HORSES IN A RURAL SETTLEMENT IN SOUTHERN BRAZIL

MOLECULAR INVESTIGATION OF HEMOTROPIC MYCOPLASMAS IN HUMAN BEINGS, DOGS AND HORSES IN A RURAL SETTLEMENT IN SOUTHERN BRAZIL

The aims of this study were to determine the prevalence of hemoplasmas in a rural Brazilian settlement’s population of human beings, their dogs and horses, highly exposed to tick bites; to identify the tick species parasitizing dogs and horses, and analyze factors associated with their infection. Blood samples from 132 dogs, 16 horses and 100 humans were screened using a pan-hemoplasma SYBR green real-time PCR assay followed by a species-specific TaqMan real-time PCR. A total of 59/132 (44.7%) dog samples were positive for hemoplasmas (21 Mycoplasma haemocanis alone, 12 ‘Candidatus Mycoplasma haematoparvum’ alone and 21 both). Only 1/100 (1.0%) human sample was positive by qPCR SYBR green, with no successful amplification of 16S rRNA or 23 rRNA genes despite multiple attempts. All horse samples were negative. Dogs >1 year of age were more likely to be positive for hemoplasmas (p = 0.0014). In conclusion, although canine hemoplasma infection was highly prevalent, cross-species hemoplasma transmission was not observed, and therefore may not frequently occur despite overexposure of agents and vectors.
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Tick-borne encephalitis virus replication, intracellular trafficking, and pathogenicity in human intestinal Caco-2 cell monolayers.

Tick-borne encephalitis virus replication, intracellular trafficking, and pathogenicity in human intestinal Caco-2 cell monolayers.

Tick-borne encephalitis virus (TBEV) is one of the most important vector-borne viruses in Europe and Asia. Its transmission mainly occurs by the bite of an infected tick. However, consuming milk products from infected livestock animals caused TBEV cases. To better understand TBEV transmission via the alimentary route, we studied viral infection of human intestinal epithelial cells. Caco-2 cells were used to investigate pathological effects of TBEV infection. TBEV-infected Caco-2 monolayers showed morphological changes including cytoskeleton rearrangements and cytoplasmic vacuolization. Ultrastructural analysis revealed dilatation of the rough endoplasmic reticulum and further enlargement to TBEV containing caverns. Caco-2 monolayers maintained an intact epithelial barrier with stable transepithelial electrical resistance (TER) during early stage of infection. Concomitantly, viruses were detected in the basolateral medium, implying a transcytosis pathway. When Caco-2 cells were pre-treated with inhibitors of cellular pathways of endocytosis TBEV cell entry was efficiently blocked, suggesting that actin filaments (Cytochalasin) and microtubules (Nocodazole) are important for PI3K- dependent (LY294002) virus endocytosis. Moreover, experimental fluid uptake assay showed increased intracellular accumulation of FITC-dextran containing vesicles. Immunofluorescence microscopy revealed co-localization of TBEV with early endosome antigen-1 (EEA1) as well as with sorting nexin-5 (SNX5), pointing to macropinocytosis as trafficking mechanism. In the late phase of infection, further evidence was found for translocation of virus via the paracellular pathway. Five days after infection TER was slightly decreased. Epithelial barrier integrity was impaired due to increased epithelial apoptosis, leading to passive viral translocation. These findings illuminate pathomechanisms in TBEV infection of human intestinal epithelial cells and viral transmission via the alimentary route.
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A case of human monocytic ehrlichiosis in Serbia

A case of human monocytic ehrlichiosis in Serbia

The disease of the humans known as humane monocytic or monocytotropic ehrlichiosis is caused by Ehrlichia chaf- feensis. It dwells and replicates in the cytoplasm of certain host cell types, mainly neutrophil leukocytes, leukocytes and monocytes, within vacuoles that are bound to cellular membrane. The name of the disease HME suggests the tropism of the organism toward peripheral blood mono- cytes [13]. Until now, only one report on HME in Serbia has been published. Dokić et al. [16] presented the case of HME in a patient admitted to Military Medical Academy. The HME is a complex zoonosis. The causing organ- ism persists in the nature through the infection of vari- ous mammals. Dogs, wolves and deer are considered to be the primary reservoirs of Ehrlichia chaffeensis. Fox and goats have been experimentally infected as well. The pri- mary vector is a tick Amblyomma americanum. Ehrlichia chaffeensis may also be transmitted by a tick Dermacentor variabilis [17]. Most ehrlichiosis cases have history of tick bites (as in our patient), although in 32% of cases this in- formation may be missing [18]. Therefore, the absence of definite tick attachment should never dissuade physician from considering the diagnosis of HME.
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Molecular detection of tick borne bacteria and protozoa in cervids and wild boars from Portugal

Molecular detection of tick borne bacteria and protozoa in cervids and wild boars from Portugal

Anaplasmoses, caused by bacteria of the genus Anaplasma, known for a long time in veterinary medicine, are also considered as emerging human diseases, and are frequently associated with infection with Anaplasma phagocytophilum [10]. This bacterium, which is the causative agent of tick-borne fever, a disease of important negative economic impact to European animal husbandry (involving domestic ruminants), also causes human granulocytic anaplasmosis. Wild ruminants are one of its main reservoirs [11] while the role of wild boars in its natural cycle is still contradictory [12]. Other Anaplasma spp. such as A. marginale and A. ovis have also been detected in European cervids [13]. In Portugal, antibodies reactive to A. phagocytophilum antigens were detected in humans and other mammals [14], while A. marginale and A. ovis were detected in cattle [15] and in sheep [16], respectively.
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Tick-borne infections in human and animal population worldwide

Tick-borne infections in human and animal population worldwide

humans, Central Asia, endophilic), Rhipicephalus sulcatus Neumann, 1908 (parasite of several orders of Mammalia, parts of central and southern Africa, Zimbabwe, Botswana, probably introduced into western Africa, exophilic) and Rhipicephalus turanicus Pomerantsev, 1936 [25]. It spreads by dwellings climbing the walls (negative geotropism) hiding in crevices and roofs, being highly reproductive and very hard to control the infestations in that all molts occur in the environment and not on host. Females lay 2000-3000 eggs in their entire lives. Unfed larvae can survive up to 8½ months, nymphs up to 6 months and adults up to 19 months. They attack any region of the host body being more frequent in the anterior limbs and in the ears causing irritation, disconfort and dermatitis. R. sanguineus sensu lato is capable of transmitting many zoonotic agents, such as tick-borne pathogens (Rickettsia rickettsii, a spotted fever agent in humans and Rickettsia conorii, a medi- terranean spotted fever agent), Babesia vogeli (canine babesiosis agent), Hepatozoon canis and Ehrlichia canis (canine monocytic ehrlichiosis agent) [26].
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Molecular detection of tick-borne bacteria and protozoa in cervids and wild boars from Portugal

Molecular detection of tick-borne bacteria and protozoa in cervids and wild boars from Portugal

Anaplasmoses, caused by bacteria of the genus Anaplasma, known for a long time in veterinary medicine, are also considered as emerging human diseases, and are frequently associated with infection with Anaplasma phagocytophilum [10]. This bacterium, which is the causative agent of tick-borne fever, a disease of important negative economic impact to European animal husbandry (involving domestic ruminants), also causes human granulocytic anaplasmosis. Wild ruminants are one of its main reservoirs [11] while the role of wild boars in its natural cycle is still contradictory [12]. Other Anaplasma spp. such as A. marginale and A. ovis have also been detected in European cervids [13]. In Portugal, antibodies reactive to A. phagocytophilum antigens were detected in humans and other mammals [14], while A. marginale and A. ovis were detected in cattle [15] and in sheep [16], respectively.
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J. Bras. Nefrol.  vol.39 número3

J. Bras. Nefrol. vol.39 número3

mayors from the major cities of the world, the 2014 joint declaration of faith leaders against modern slavery, and the Magisterium of Pope Francis, who in June 2016, at the Judges’ Summit on Human Trafficking and Organized Crime, stated that organ traffick- ing and human trafficking for the purpose of organ removal are “true crimes against humanity [that] need to be recognized as such by all religious, political and social leaders, and by national and international legislation,” we, the undersigned partici- pants of the Pontifical Academy of Sciences Summit on Organ Trafficking, resolve to combat these crimes against humanity through comprehensive efforts that involve all stakeholders around the world.
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Hist. cienc. saudeManguinhos  vol.14 suppl.

Hist. cienc. saudeManguinhos vol.14 suppl.

According to Hill’s description (1987), the ritual is divided into three stages. In the first, the visitors play a variety of wind instruments and perform an elaborate set of dances, in which ordered pairs of men and women circle about the food. These performances are said to be a stylized imitation of the reproductive behavior of the aracu, a species of Leporinus fish. In the second stage, based on imitation of the eating and mating behavior of déetu, or coconut palm weevils, the hosts accept the food and then invite the visitors into their house. This moment marks the beginning of a social interaction where food and drink are shared and all perform together inside the house. At the same time, some male guests remain outside, playing long déetu flutes, with their ends pointing into the eaves of the house. This performance symbolizes the overcoming of the society’s inner and outer boundaries. Lastly, in the third stage, after hosts and guests have engaged in reciprocal exchanges of food and drink, in an atmosphere of familiarity and informality they perform improvised songs and chants—which also represent the behavior of fish and other animals—eradicating any distinction between guest and host.
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Assessment Of NPK In Human Male And Female Urine For Its Fertilising Potential In Agriculture

Assessment Of NPK In Human Male And Female Urine For Its Fertilising Potential In Agriculture

discharge into water is reduced by about 60% irrespective of the type of treatment [10]. Pure urine is sterile but there is the likelihood of cross-contamination with the use of urine separating (Ecosan) toilets [28]. According to Jönsson et al. (2000) separated urine contains a greater part of the total nutrients in normal sewage; 80% of N, 55% of P, and 60% of K in just 1.5% of the volume of the sewage. According to Rheiberger (1936), there are comparable levels of creatine, urea and ammonia nitrogens in urine among primates such as man, mangabeys, baboons and chimpanzees. However, he identified sex differences in creatinine nitrogen coefficients of the male mangabeys, baboons and chimpanzees to be higher than those in the female counterparts. In small cases there was reversal of the magnitude seen in the macaques species precluding an assumption as to the validity of the observation. In analysing sex differences in urine with respect to lysine and α - amino nitrogen, the mean excretion of α - amino nitrogen whether ―total,‖ ―free,‖ or ―bound,‖ was higher for females than for males [22]. Thus, it is possible that the higher rate of amino acid excretion observed in females might be correlated with the sexual cycle, although no evidence of this was observed in the case of the four amino acids studied by Thompson and Kirby (1949) when samples from the same subjects were taken at various stages of the menstrual cycle. The influence of sex (gender) on the level of NPK in human urine has received no attention. Therefore, there is a need to study the effect from the Ecological Sanitation (ECOSAN) perspective, especially under local conditions. This is because gender ECOSAN urinals are going to spring up with the advent of industries and ECOSAN concepts, especially in the developing countries. The use of urine in agriculture has been studied in countries such as Sweden, Germany, Switzerland, South Africa, Burkina Faso and Nigeria. In all these studies, the fertilizing ability of human urine was established as being comparable to that of chemical fertilizers, such as 21% N ammonia. However, in Ghana little U
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Rev. Bras. Reumatol.  vol.49 número5 en v49n5a01

Rev. Bras. Reumatol. vol.49 número5 en v49n5a01

LD patients were tested. Additionally, PCR results always gave negative results when speciic or conserved primers to identify B. burgdorferi sensu stricto or genus Borrelia were employed. Another important feature observed with Brazilian LD patients was the appearance of strong autoimmunity as antibodies directed to extract of human brain cells membrane or extract of human skin (commercial products from Sigma Co.). At this point, we understood that Brazilian LD was completely different from classical LD, and we found many dificulties to report our results. The manuscripts from our group were always refuted to be published by International Journals , because revisers never accepted the clinical and laboratorial indings described in our patients.
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Rev. Soc. Bras. Med. Trop.  vol.49 número5

Rev. Soc. Bras. Med. Trop. vol.49 número5

Arboviruses impose a serious threat to public health services. We report a case of a patient returning from a work trip to the Amazon basin with myalgia, arthralgia, fever, and headache. During this travel, the patient visited riverside communities. Both dengue and Chikungunya fevers were irst suspected, tested for, and excluded. Mayaro fever was then conirmed by reverse transcription polymerase chain reaction followed by next-generation sequencing and phylogenetic reconstruction. The increased awareness of physicians and consequent detection of Mayaro virus in this case was only possible due a previous surveillance program with speciic health personnel training about these neglected arboviruses.
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Estudo da reatividade cruzada em amostras de soro de cães positivos para Leishmania sp., Babesia canis e Ehrlichia canis, pelo ensaio imunoenzimático indireto e pela reação de imunofluorescência indireta

Estudo da reatividade cruzada em amostras de soro de cães positivos para Leishmania sp., Babesia canis e Ehrlichia canis, pelo ensaio imunoenzimático indireto e pela reação de imunofluorescência indireta

Jaboticabal is until now considered non-endemic for visceral leishmaniasis. Though, the study of cross-reaction between E. canis and B. canis with visceral leishmaniasis became more feasibility, since antibodies against Leishmania sp. in dogs from Jaboticabal are not expected. The four dogs, with reaction to Leishmania sp. in the first ELISA in EL nearly to the cut-off point, which suggests a repetition of the test and the performance of other tests to confirm positivity, were retested by the same assay and IFAT, turning out to be negative. None of these dogs had clinical signs or positive parasitological isolation.
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Amblyomma americanum as a Bridging Vector for Human Infection with Francisella tularensis.

Amblyomma americanum as a Bridging Vector for Human Infection with Francisella tularensis.

Of particular interest for our study is the potential for A. americanum to serve as an over- wintering reservoir for F. tularensis in its sylvatic cycle by maintenance of colonization in nymphs which constitute the primary A. americanum stage that survives overwintering in the south-central U.S. endemic region [12]. From our study, A. americanum infected as larvae exhibited potential to maintain prolonged colonization as unfed nymphs compatible with over- wintering. This observation is consistent with Hopla’s earlier observations in which he infected larvae and determined their quanta of infection through the adult stage by subsequent feeding on uninfected guinea pigs to molt infect larvae to nymphs and adults [23]. Hopla reported sim- ilar quanta of infection in engorged larvae and unfed nymphs to quanta that we observed in 1 day post-capillary feeding larvae and 14 day post-molting nymph of log 4 and 5, respectively. Hopla refed these unfed nymphs molted from infected larvae immediately following molting such that there is no comparable data for persistence of F. tularensis unfed nymphs in his study to assess potential for overwintering of the agent in unfed nymphs. From our study, we observed that F. tularensis persisted in unfed A. americanum nymphs for up to 168 days post- capillary feeding (147 days post molting), which was the longest sampling time. However, the tissue distribution of F. tularensis in unfed A. americanum nymphs changed from gut and sali- vary glands at 19 days after molting to primarily gut at 147 days post-molt. It would appear that F. tularensis would have to re-disseminate to salivary glands for the nymphs to be infective for initiating the next seasonal cycle. There is some evidence from Hopla’s studies and for other tick and pathogens that refeeding does elicit pathogen secretion [23–26].
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Molecular detection and characterization of tick-borne pathogens in dogs and ticks from Nigeria.

Molecular detection and characterization of tick-borne pathogens in dogs and ticks from Nigeria.

Several tick-borne bacteria and parasites are important pathogens of humans and animals [1]. Being haematophagous, ticks are capable of transmitting disease agents such as viruses, bacteria and protozoa. Historically, they have been considered second only to mosquitoes in their ability to transmit disease agents [2]. Ticks attach to their hosts, facilitating transmission of infectious agents to the host and their spread to different geographical regions via traveling pets or other means of transportation [3]. Globalization and increased international trade, urbanization, climate change and increased travel and mobility of pets have resulted in rapid extension of the zoogeographical range for many tick species [1]. In areas where canine vector-borne diseases are endemic, dogs can be simultaneously or sequentially infected with more than one vector-borne agent [3,4]. Because blood sucking vectors contain infected host blood and pathogens, they are reliable indicators for the existence of pathogens in a specific area [5]. Therefore, it is recommended to periodically screen animals and vectors for pathogen carriage.
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Molecular and serological detection of tick-borne pathogens in dogs from an area endemic for Leishmania infantum in Mato Grosso do Sul, Brazil

Molecular and serological detection of tick-borne pathogens in dogs from an area endemic for Leishmania infantum in Mato Grosso do Sul, Brazil

The ELISA method employed here was described in detail by Oliveira et al. (2008). Briefly, 100 mL of crude Leishmania sp. antigen diluted in 0.05M sodium carbonate-bicarbonate buffer (pH 9.6) was added to each well on ELISA plates (Nunclon TM surface; Nunc, Denmark) and 5mg mL protein concentration was used. After overnight incubation at 4 °C, the plates were washed three times with 0.05% PBS Tween-20. The plates were blocked with 200 mL containing 6% skim milk for 2 hours at 37 °C to reduce nonspecific binding. The blocking agent was removed, and individual dog serum diluted (1:400) in PBS Tween-20 with 5% skim milk added to each well, followed by incubation for 90 minutes at 37 °C and washing as described above. One hundred mL of alkaline phosphatase conjugated anti-dog IgG (Sigma-Aldrich, St. Louis, USA) diluted at 1: 4.000 in PBS Tween-20 with 5% normal rabbit serum was added to each well, followed by incubation for 90 minutes at 37 °C. The plates were washed and the substrate (p-nitrophenyl phosphate) diluted in diethanolamine buffer, pH 9.8, was added. Absorbance at 405 nm was read after 45 minutes of incubation at room temperature, using an ELISA reader (Dynex Technologies, USA). The discriminating absorbance value (cut-off) was determined as being 2.5 times the mean absorbance value of the negative control.
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Influence of the biotope on the tick infestation of cattle and on the tick-borne pathogen repertoire of cattle ticks in Ethiopia.

Influence of the biotope on the tick infestation of cattle and on the tick-borne pathogen repertoire of cattle ticks in Ethiopia.

The study area is situated in South-Western Ethiopia, along the Didessa valley (in the region between Nekemte and Jima, coordinates: 09u059N, 36u339E–7u409N, 36u50E). Three types of habitats (biotopes) were selected for tick collection. These biotopes have different altitude, rainfall, relative humidity, temperature, vegetation coverage, wildlife, cultivated crops and livestock animals. Ticks were collected from cattle between June-July of 2012 in the following biotopes: (A) moist highland (above 1500 m altitude, in excess of 900 mm rain annually, temperature 18– 20 uC, with dense forest vegetation); (B) mid highland (less moist and cool, with mixed vegetation coverage showing altitudinal change); (C) savannah lowland (500–1500 m altitude, annual rainfall below 900 mm, temperature 18–24 uC, with shrubs, gallery forests around rivers, woodland). Ticks were removed with strong pointed forceps from the skin of 109 cattle (35, 56 and 18 animals according to the above three biotope types, respectively) in 18 herds. Because this was part of the regular veterinary care and the field studies did not involve endangered or protected species, no specific permissions were required for these activities. All specimens were put into 70% ethanol in a separate vial according to host animal, and stored consequently at around room temperature.
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Rev. Bras. Hematol. Hemoter.  vol.34 número6

Rev. Bras. Hematol. Hemoter. vol.34 número6

Research on human beings has expanded greatly due to progress and the evolution of society as well as customs. Not only the unceasing development of research on human beings, but also interference in the beginning and end of life with homologous and heterogonous human reproduction, surrogate motherhood, cloning, gene therapies, eugenics, euthanasia, dysthanasia, orthothanasia, assisted suicide, genetic engineering, reassignment surgery in cases of transsexuality, the use of recombinant DNA technology and embryonic stem cells, transplantation of human organs and tissues, biotechnology and many other scientiic advances. Scientiic progress goes faster than the real needs of human beings, who are the inal recipient of the entire evolutionary progress. Hence, there is the need to scrutinize whether new technologies are necessary, suitable and timely so that humanity can achieve its postulate of bene vivere. Human cloning, as an abrupt scientiic fact, has presented itself to the world community as a procedure that can be performed with relative success and with little dificulty, since it achieved its objectives with the cloning of Dolly the sheep. This issue became the topic of discussion not only in the scientiic community but in the lay population, and it received from both, global disapproval. The conclusion is that the human being is unique, with a life cycle deined by the rules of nature. Reversal will cause a violation of the genetic heritage and, above all, will confront the constitutional principle of human dignity.
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