The effect of Lucilia sericata larval excretion/secretion (ES) products on cellular responses in wound healing.

Chronic wounds are still regarded as a serious public health concern, which are on the increase mainly due to the changes in life styles and aging of the human population. There are different types of chronic wounds, each of which requires slightly different treatment strategies. Nevertheless, wound bed preparation is included in treatment of all types of chronic wounds and involves tissue debridement, inflammation, and infection control, as well as moisture balance and epithelial edge advancement. Maggot therapy (MT) is a form of biological debridement which involves the application of live medical grade Lucilia sericata (Meigen, 1826) (Diptera: Calliphoridae) larvae. Whereas it was initially thought to act mainly through debridement, today MT is known to influence all four overlapping physiological phases of wound repair: homeostasis, inflammation, proliferation, and remodelling/maturing. During MT, medical-grade larvae are applied either freely or enclosed in tea-bag like devices (biobag) inside the wounds, which suggests that larva excretion/secretion (ES) products can facilitate the healing processes directly without the need of direct contact with the larvae. This review summarizes the relevant literature on ES-mediated effects on the cellular responses involved in wound healing.

Bibliometric analysis of publications on house dust mites during 1980-2018.

BACKGROUND: The global prevalence of allergic diseases has increased dramatically in recent years and are now recognized as significant chronic diseases worldwide. One of the most important allergens that causes allergic diseases is house dust mites. OBJECTIVE: This study aims to present a bibliometric overview of research published on dust mites between 1980 and 2018. METHODS: Articles published from 1980 to 2018 were analyzed using bibliometric methods. The keywords "Dust mite*," and "Dermatophagoides" were used in the Web of Science (WoS). Simple linear regression analysis was used to estimate the number of future publications on this subject. RESULTS: A total of 4742 publications were found, 2552 (53.8%) of them were articles. Most of the articles were on subjects related to immunology (1274; 49.9%) and allergy (1229; 48.1%). Clinical and Experimental Allergy (222; 8.7%) was the journal with the most publications. The USA was the country that most contributed to the literature with 461 (18.1%) articles. The countries producing the most publications on this subject were developed countries. The most active author was W.R. Thomas (66; 2.5%). The most productive institution was the University of Western Australia (91; 3.6%). The most cited article was published in the New England Journal of Medicine. CONCLUSION: According to the findings, developed countries were the most productive in publishing on house dust mites. By planning multinational research rather than regional studies, it may be suggested that researchers in underdeveloped or developing countries could also conduct more research on this subject.

Potential tick vectors for Theileria equi in Israel.

Theileria equi Mehlhorn and Schein, 1998 (Piroplasmida: Babesiidae) is an important tick-borne pathogen of horses that is highly endemic in many parts of the world, including Israel. The present study evaluated the potential roles of five hard tick species [Hyalomma excavatum Koch, 1844; Hyalomma marginatum Koch, 1844; Rhipicephalus turanicus Pomerantsev 1936; Rhipicephalus annulatus Say, 1821; Haemaphysalis parva (Neumann, 1897) (all: Ixodida: Ixodidae)], previously found to infest horses in Israel, in acting as vectors for piroplasmosis. For this, DNA was extracted from whole ticks and, when possible, from the salivary glands in each species (n = 10-59). Polymerase chain reaction amplification and sequencing of the 18S rRNA gene were used to detect T. equi in 48 of the 127 ticks (37.8%) and in 21 of the 90 extracted salivary glands (23.3%) in all five species. All but two sequences were classified as T. equi genotype A; the remaining two were classified as genotype D. The findings of this study point to Ha. parva and R. annulatus as potential novel vectors of T. equi, and suggest that parasite genotype selection occurs within the tick vector.

Overview and features of larval developmental sites of biting midges species associated with livestock in Israel with implications to their control.

The larval developmental sites of Culicoides species were assessed from 1155 samples collected during the years 1969-2003. Culicoides circumscriptus was most prolific in mud with medium organic matter with proportional representation of 55.8%. Culicoides imicola breeds mainly in damp mixture of rotten, decomposed animal dung with or without some mud, with proportional representation of 97.2%. Culicoides obsoletus was found mostly in rotten banana stumps, with proportional representation of almost 100%. Culicoides puncticollis was found in mud with a medium amount of organic matter with proportional representation of 35.6%. Culicoides distinctipennis showed 22.2% proportional representation for mud poor in organic matter. Culicoides schultzei gr. was most prolifically in mud rich in organic matter with proportional representation of 6.2%. Culicoides cataneii was most prolifically in mud with a medium amount of organic matter with proportional representation of 1.8%. Maximum duration time to emergence from the larval developmental sites ranged from seven weeks in C. obsoletus to fourteen weeks in C. circumscriptus and nine weeks in C. imicola. All the studied species breed throughout the year. Significant innate differences in the proportions of the sexes were found in the emergence of six species.

Molecular detection of zoonotic bartonellae (B. henselae, B. elizabethae and B. rochalimae) in fleas collected from dogs in Israel.

Fleas represent an acknowledged burden on dogs worldwide. The characterization of flea species infesting kennel dogs from two localities in Israel (Rehovot and Jerusalem) and their molecular screening for Bartonella species (Rhizobiales: Bartonellaceae) was investigated. A total of 355 fleas were collected from 107 dogs. The fleas were morphologically classified and molecularly screened targeting the Bartonella 16S-23S internal transcribed spacer (ITS). Of the 107 dogs examined, 80 (74.8%) were infested with Ctenocephalides canis (Siphonaptera: Pulicidae), 68 (63.6%) with Ctenocephalides felis, 15 (14.0%) with Pulex irritans (Siphonaptera: Pulicidae) and one (0.9%) with Xenopsylla cheopis (Siphonaptera: Pulicidae). Fleas were grouped into 166 pools (one to nine fleas per pool) according to species and host. Thirteen of the 166 flea pools (7.8%) were found to be positive for Bartonella DNA. Detected ITS sequences were 99-100% similar to those of four Bartonella species: Bartonella henselae (six pools); Bartonella elizabethae (five pools); Bartonella rochalimae (one pool), and Bartonella bovis (one pool). The present study indicates the occurrence of a variety of flea species in dogs in Israel; these flea species are, in turn, carriers of several zoonotic Bartonella species. Physicians, veterinarians and public health workers should be aware of the presence of these pathogens in dog fleas in Israel and preventive measures should be implemented.

Molecular detection of Rickettsia aeschlimannii in Hyalomma spp. ticks from camels (Camelus dromedarius) in Nigeria, West Africa.

Several species of the spotted fever group rickettsiae have been identified as emerging pathogens throughout the world, including in Africa. In this study, 197 Hyalomma ticks (Ixodida: Ixodidae) collected from 51 camels (Camelus dromedarius) in Kano, northern Nigeria, were screened by amplification and sequencing of the citrate synthase (gltA), outer membrane protein A (ompA) and 17-kDa antigen gene fragments. Rickettsia sp. gltA fragments were detected in 43.3% (42/97) of the tick pools tested. Rickettsial ompA gene fragments (189 bp and 630 bp) were detected in 64.3% (n = 27) and 23.8% (n = 10) of the gltA-positive tick pools by real-time and conventional polymerase chain reaction (PCR), respectively. The amplicons were 99-100% identical to Rickettsia aeschlimannii TR/Orkun-H and R. aeschlimannii strain EgyRickHimp-El-Arish in GenBank. Furthermore, 17-kDa antigen gene fragments of 214 bp and 265 bp were detected in 59.5% (n = 25) and 38.1% (n = 16), respectively, of tick pools, and sequences were identical to one another and 99-100% identical to those of the R. aeschlimannii strain Ibadan A1 in GenBank. None of the Hyalomma impressum ticks collected were positive for Rickettsia sp. DNA. Rickettsia sp. gltA fragments (133 bp) were detected in 18.8% of camel blood samples, but all samples were negative for the other genes targeted. This is the first report to describe the molecular detection of R. aeschlimannii in Hyalomma spp. ticks from camels in Nigeria.

Bartonella species in fleas from Palestinian territories: prevalence and genetic diversity.

Bartonellosis is an infectious bacterial disease. The prevalence and genetic characteristics of Bartonella spp. in fleas of wild and domestic animals from Palestinian territories are described. Flea samples (n=289) were collected from 121 cats, 135 dogs, 26 hyraxes and seven rats from northern (n=165), central (n=113), and southern Palestinian territories (n=11). The prevalent flea species were: Ctenocephalides felis (n=119/289; 41.2%), Ctenocephalides canis (n=159/289; 55%), and Xenopsylla sp. (n=7/289; 2.4%). Targeting the Intergenic Transcribed Spacer (ITS) locus, DNA of Bartonella was detected in 22% (64/289) of all fleas. Fifty percent of the C. felis and 57% of the Xenopsylla sp. contained Bartonella DNA. DNA sequencing showed the presence of Bartonella clarridgeiae (50%), Bartonella henselae (27%), and Bartonella koehlerae (3%) in C. felis. Xenopsylla sp. collected from Rattus rattus rats were infected with Bartonella tribocorum, Bartonella elizabethae, and Bartonella rochalimae. Phylogenetic sequence analysis using the 16S ribosomal RNA gene obtained four genetic clusters, B. henselae and B. koehlerae as subcluster 1, B. clarridgeiae as cluster 2, while the rat Bartonella species (B. tribocorum and B. elizabethae) were an outgroup cluster. These findings showed the important role of cat and rat fleas as vectors of zoonotic Bartonella species in Palestinian territories. It is hoped that this publication will raise awareness among physicians, veterinarians, and other health workers of the high prevalence of Bartonella spp. in fleas in Palestinian territories and the potential risk of these pathogens to humans and animals in this region.

Ectoparasites in urban stray cats in Jerusalem, Israel: differences in infestation patterns of fleas, ticks and permanent ectoparasites.

In a period cross-sectional study performed to examine ectoparasites on 340 stray cats in Jerusalem, Israel, 186 (54.7%) were infested with the cat flea, Ctenocephalides felis (Siphonaptera: Pulicidae), 49 (14.4%) with the cat louse, Felicola subrostratus (Phthiraptera: Trichodectidae), 41 (12.0%) with the ear mite, Otodectes cynotis (Astigmata: Psoroptidae), three (0.9%) with the fur mite, Cheyletiella blakei (Trobidiformes: Cheyletidae), two (0.6%) with the itch mite Notoedres cati (Astigmata: Sarcoptidae), and 25 (7.3%) with ticks of the species Rhipicephalus sanguineus sensu lato (Ixodida: Ixodidae), Rhipicephalus turanicus or Haemaphysalis adleri (Ixodida: Ixodidae). A higher number of flea infestations was observed in apparently sick cats (P < 0.05) and in cats aged < 6 months (P < 0.05). The proportion of flea-infested cats (P < 0.01), as well as the number of fleas per infested cat (P < 0.01), was higher in autumn than in other seasons. By contrast with findings in cats with flea infestations, rates of infestation with ticks were higher amongst cats with clinical signs (P < 0.01) and cats aged ≥ 6 months (P < 0.05). The high rates of ectoparasite infestation in the cats studied constitute a risk for the spread of vector-borne infections of zoonotic and veterinary importance.

Pain related to maggot debridement therapy.

OBJECTIVE: To summarise our experience with maggot debridement therapy (MDT) in relation to pain observed in patients treated in 16 departments and units of the Hadassah Hospital in Jerusalem, Israel. METHOD: A secondary analysis of data from 435 patients. Maggots were either placed directly on the wound using a cage-like dressing (DA), or they were applied to the wound encased in a previously prepared hermetic tea-bag like pouch (TBA). During each treatment, patients were asked whether they felt any difference in the level of pain before and during MDT treatment. RESULTS: Overall, 165 patients (38%) reported increased pain during MDT. Seventeen patients (41%), who were treated with the TBA technique, and 148 patients (38%), who were treated with the DA technique, reported increased pain and were treated with analgesics before or during MDT. In five patients, the treatment had to be discontinued due to uncontrolled pain during MDT. Pain control measures were undertaken in patients who were already in intense pain prior to the initiation of MDT and in those patients who reported intense pain during DA treatment. The measures included shorter periods of application of maggots, use of the TBA rather than DA technique, and applying relatively small maggots as well as a smaller number of maggots during an MDT session. In patients who continued reporting intense pain, systemic analgesic medications and peripheral nerve blocks were used. CONCLUSION: Since a full debridement requires an average of 2-3 maggot cycles, which last 3-5 days, and since a large percentage of patients treated with MDT complain of pain that may last throughout the therapy period, it is deemed worthwhile and even essential to titrate analgesics as needed and be prepared to treat patients even with potent analgesics, such as opioids. In cases when pain is intense and uncontrolled with systemic medications, peripheral nerve blocks should be considered. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no conflicts of interest to declare.

The use of maggot debridement therapy in the treatment of chronic wounds in hospitalised and ambulatory patients.

OBJECTIVE: To summarise our experience of the use of medicinal maggots for the debridement of necrotic chronic wounds and to try and identify prognostic factors for debridement success and associated pain. METHOD: During the years 1996­2009, 723 wounds of 435 patients (180 females and 255 males) were treated with maggot debridement therapy (MDT) in 16 departments and units of the Hadassah Hospital in Jerusalem, Israel. Overall, 261 patients were treated during hospitalisation, while 174 were treated as ambulatory patients. In 90.5% of the patients the wounds were located on the leg, but only 48.0% had diabetic foot ulcers. The wound duration range from one to 240 months (mean=8.9; median=4 months). Sterile maggots of the green bottle fly, Lucilia sericata, were used for MDT. In 90.6% of the cases, maggots were placed directly on the wound using a cage-like dressing and left for 24 hours, while in 9.4% of the patients maggots concealed in a tea-bag like polyvinyl netting were used. The concealed maggots were left on the wound for 2­3 days. RESULTS: The number of treatments was 1­48 (mean=2.98; median=2) and the duration of the treatment varied between one and 81 days (mean=4.65; median=3). In 357 patients (82.1%) complete debridement of the wound was achieved, while in 73 patients (16.8%) the debridement was partial and in five (1.1%) it was ineffective. Increased pain or discomfort during MDT were reported in 38% of the patients. CONCLUSION: MDT is a very safe, simple and effective treatment modality for chronic wounds in ambulatory and hospitalised patients. DECLARATION OF INTEREST: There were no external sources of funding for this study. The authors have no additional conflicts of interest to declare.

Crossbreeding between different geographical populations of the brown dog tick, Rhipicephalus sanguineus (Acari: Ixodidae).

Brown dog ticks are distributed world-wide, and their systematics and phylogeny are the subject of an ongoing debate. The present study evaluates the reproductive compatibility between Rhipicephalus sanguineus ticks from North America, Israel, and Africa. Female ticks of the parent generation were mated with males from the same and alternate colonies. Every pure and hybrid cohort was maintained separately into the F2 generation with F1 females being allowed to mate only with males from the same cohort. The following survival parameters were measured and recorded for every developmental stage: feeding duration and success; engorgement weight, fertility, and fecundity of females; molting and hatching success. Ticks from North American and Mediterranean populations hybridized successfully. The survival parameters of all their hybrid lines were similar to those in pure lines throughout the F1 generation, and F1 adults were fully fertile. Parent adult ticks from the African population hybridized with either North American or Mediterranean ticks and produced viable progenies whose survival parameters were also similar to those in pure lines throughout the F1 generation. However, F1 adults in the four hybrid lines that included African ancestry were infertile. No parthenogenesis was observed in any pure or hybrid lines as proportion of males in F1 generation ranged from 40 to 60 %. Phylogenetic analysis of the 12S rDNA gene sequences placed African ticks into a separate clade from those of the North American or Mediterranean origins. Our results demonstrate that Rh. sanguineus ticks from North America and Israel represent the same species, whereas the African population used in this study is significantly distant and probably represents a different taxon.

Molecular detection of Rickettsia massiliae, Rickettsia sibirica mongolitimonae and Rickettsia conorii israelensis in ticks from Israel.

Rickettsioses are recognized as important emerging vector-borne infections of humans worldwide. Previous reports documented the presence of two spotted fever group rickettsiae in Israel, Rickettsia conorii israelensis and Rickettsia felis. The aim of this study was to characterize the diversity of rickettsiae in ticks collected from vegetation and the ground, from different parts of Israel. Non-engorged questing adult ticks were collected from 13 localities. A total of 131 tick pools, 83 of Rhipicephalus turanicus and 48 of Rhipicephalus sanguineus (each with 2-10 ticks per pool), were included in this study. In addition, 13 Hyalomma sp. ticks were collected. The ticks were molecularly screened for rickettsiae, targeting the citrate synthase (gltA) and the outer membrane protein A (ompA) gene loci. Rickettsia massiliae ompA DNA (100% sequence identity; 180 bp) was detected in 32 Rh. turanicus and 12 Rh. sanguineus tick pools. R. conorii israelensis was detected in three Rh. sanguineus pools. Rickettsia sibirica mongolitimonae ompA DNA (100% sequence identity; 182 bp) was found in one Hyalomma tick. This study reports the first detection of R. massiliae and R. sibirica mongolitimonae in ticks from Israel. This is the first report describing the presence of these human pathogens in the Middle East.

Molecular detection of Ehrlichia canis, Anaplasma bovis, Anaplasma platys, Candidatus Midichloria mitochondrii and Babesia canis vogeli in ticks from Israel.

: Ticks are vectors of important pathogens of human and animals. Therefore, their microbial carriage capacity is constantly being investigated. The aim of this study was to characterize the diversity of domestic animal pathogens in ticks collected from vegetation and the ground, from different parts of Israel. Non-engorged questing adult ticks were collected from 13 localities. A total of 1196 ticks in 131 pools-83 pools of Rhipicephalus turanicus and 48 of Rhipicephalus sanguineus (with two to ten ticks per pool)-were included in this study. In addition, 13 single free-roaming Hyalomma spp. ticks were collected. Screening by molecular techniques revealed the presence of Ehrlichia canis, Anaplasma platys, Anaplasma bovis and Babesia canis vogeli DNA in R. turanicus ticks. E. canis, A. bovis, B. canis vogeli and Candidatus Midichloria mitochondrii DNA sequences were detected in R. sanguineus ticks. Candidatus Midichloria mitochondrii DNA was also detected in Hyalomma spp. ticks. Neither Hepatozoon spp. nor Bartonella spp. DNA was detected in any of the ticks examined. This study describes the first detection of E. canis in the tick R. turanicus, which may serve as a vector of this canine pathogen; E. canis was the most common pathogen detected in the collected questing ticks. It also describes the first detection of A. bovis and Candidatus Midichloria mitochondrii in Israel. To the best of the author's knowledge, this is the first report describing the detection of DNA of the latter two pathogens in R. sanguineus, and of A. bovis in R. turanicus.

Effects of blood type and blood handling on feeding success, longevity and egg production in the body louse, Pediculus humanus humanus.

The effects of feeding different types of human blood to human body lice, Pediculus humanus humanus L. (Phthiraptera: Pediculidae), on feeding success, longevity and numbers of eggs laid were investigated using an artificial blood-feeding system in the laboratory. No significant differences were found between lice fed on different human blood types for any of the parameters tested. However, when lice were fed on human blood of one blood type followed immediately by a different blood type, they took significantly smaller bloodmeals, their longevity was reduced and they laid fewer eggs per female than control lice that had been fed twice on the same human blood type. When lice were fed human blood that had been stored for 1-26 weeks, the quantity of blood taken, the proportion of lice that became fully engorged and lice longevity diminished gradually as the storage time of the blood increased, but there was no effect of storage time on the mean number of eggs laid per female. However, lice would not feed on 26-week-old blood. The type of anticoagulant used had a significant effect on the proportion fed, longevity and number of eggs laid per female. Generally, EDTA (ethylenediaminetetraacetic acid)-treated blood reduced longevity and the number of eggs laid per female to a greater degree than heparinized or citrated blood. Lice fed on rabbit blood took significantly larger amounts of blood, lived longer and laid a higher mean number of eggs per female than lice fed on human blood.

Co-feeding as a route for transmission of Rickettsia conorii israelensis between Rhipicephalus sanguineus ticks.

Rickettsia conorii is widely distributed in Europe, Asia, and Africa. The brown dog tick, Rhipicephalus sanguineus, is the recognized vector of R. conorii. In this study, we assessed the efficiency of R. conorii israelensis transmission between co-feeding Rh. sanguineus ticks. Infected Rh. sanguineus adults and uninfected nymphs were fed simultaneously upon either naïve dogs or a dog previously exposed to this agent. When ticks were placed upon naïve dogs, 92-100% of nymphs acquired the infection and 80-88% of infected engorged nymphs transmitted it transstadially. When ticks were placed upon a seropositive dog, only 8-28.5% of recipient nymphs became infected. Our results establish the first evidence for efficient natural transmission of R. conorii israelensis between co-feeding ticks upon both naïve and seropositive dogs. This route of transmission can ensure continuous circulation of R. conorii israelensis in tick vectors even in the absence of naïve reservoir hosts.

Elimination of symbiotic Aeromonas spp. from the intestinal tract of the medicinal leech, Hirudo medicinalis, using ciprofloxacin feeding.

The use of the medicinal leech (Hirudo medicinalis) in promoting venous drainage in tissues whose vitality is threatened by venous congestion and obstruction, especially in plastic and reconstructive surgery, has been complicated by infections caused by Aeromonas spp. These are leech endosymbionts for which patients undergoing hirudotherapy frequently receive systemic chemoprophylaxis. In order to evaluate the possibility of rendering leeches safe for use on patients, H. medicinalis were fed artificially with a 2 g/L arginine solution (used as a phagostimulant) supplemented with ciprofloxacin (100 mg/L). Aeromonads were detected in 57 out of 80 control leeches (71.3%), but in none of the 56 leeches treated with ciprofloxacin (p <0.001). Treated leeches survived for up to 4 months. Tested weekly, 61% of these leeches took human blood for at least 4 weeks after treatment and all remained negative for aeromonads. All water samples in which leeches were kept before treatment were contaminated with Aeromonas spp.; none were detected in any of the NaCl/arginine solutions with which treated animals were fed. Molecular characterization of two phenotypically distinct isolates using gyrB sequencing showed that one clustered tightly with A. veronii and the other was closely related to A. media. Other environmental bacteria and fungi were isolated from 26.5% of treated leeches that had taken a blood meal 1-4 weeks after treatment. Ciprofloxacin reduced the number of leech-associated aeromonads to undetectable levels for extended periods. Most treated leeches were ready to take a blood meal after treatment, suggesting the possibility of using ciprofloxacin-treated leeches instead of chemoprophylaxis in patients undergoing hirudotherapy.

Incongruent effects of two isolates of Rickettsia conorii on the survival of Rhipicephalus sanguineus ticks.

Rickettsia conorii, the etiologic agent of Mediterranean spotted fever is widely distributed in Southern Europe, the Middle East, Africa, India and the Caspian region. In the Mediterranean region, the brown dog tick, Rhipicephalus sanguineus, is the recognized vector of R. conorii. To study tick-pathogen relationships and pathogenesis of infection caused in model animals by the bite of an infected tick, we attempted to establish a laboratory colony of Rh. sanguineus persistently infected with R. conorii. Rhipicephalus sanguineus ticks of North American and Mediterranean origin were exposed to R. conorii isolates of African (R. conorii conorii strain Malish) and Mediterranean (R. conorii israelensis strain ISTT) origin. Feeding of ticks upon infected mice and dogs, intra-hemocoel inoculation, and submersion in suspensions of purified rickettsiae were used to introduce the pathogen into uninfected ticks. Feeding success, molting success and the longevity of molted ticks were measured to assess the effects of R. conorii on the survival of Rh. sanguineus. In concordance with previously published results, Rh. sanguineus larvae and nymphs from both North American and Mediterranean colonies exposed to R. conorii conorii Malish experienced high mortality during feeding and molting or immediately after. The prevalence of infection in surviving ticks did not exceed 5%. On the other hand, exposure to ISTT strain had lesser effect on tick survival and resulted in 35-66% prevalence of infection. Rh. sanguineus of Mediterranean origin were more susceptible to infection with either strain of R. conorii than those from North America. Previous experimental studies had demonstrated transovarial and transstadial transmission of R. conorii in Rh. sanguineus; however, our data suggest that different strains of R. conorii may employ different means of maintenance in nature. The vertebrate host may be a more important reservoir than previously thought, or co-feeding transmission between different generations of ticks may obviate or lessen the requirement for transovarial maintenance of R. conorii.

Treatment of scabies infestations.

Scabies is an intensely pruritic disorder induced by an immune allergic response to infestation of the skin by the mite Sarcoptes scabiei. The biology of the mite, the clinical aspects and diagnosis of scabies infestations as well as the treatment of choice with 5% permethrin dermal cream and the use of scabicides based on other chemical substances are reviewed.

Antibacterial substances of low molecular weight isolated from the blowfly, Lucilia sericata.

Low molecular weight compounds were isolated by high-performance liquid chromatography from the maggot or haemolymph extracts of Lucilia sericata (Meigen) (Diptera: Calliphoridae). Using gas chromatography-mass spectrometry analysis, three compounds were obtained: p-hydroxybenzoic acid (molecular weight 138 Da), p-hydroxyphenylacetic acid (molecular weight 152 Da) and octahydro-dipyrrolo[1,2-a;1',2'-d] pyrazine-5,10-dione (molecular weight 194 Da), also known as the cyclic dimer of proline (or proline diketopiperazine or cyclo[Pro,Pro]). All three molecules revealed antibacterial activity when tested against Micrococcus luteus and/or Pseudomonas aeruginosa, and the effect was even more pronounced when these molecules were tested in combination and caused lysis of these bacteria.