Neutralizing based seroprevalence study of Toscana virus in livestock from Algeria.

Toscana virus is a sandfly-borne human pathogen belonging to Phlebovirus genus into Phenuiviridae family. It is emerging in north Africa posing a complex threat to public health. TOSV is heavily affecting sandfly-exposed people in northern Algeria. A larger distribution has recently been stated in Algeria by using dog sera. Dog exposure to TOSV was repeatedly identified in north Algeria, with 4.56% lately detected to possess respective neutralizing antibodies. However, evidence for TOSV has only been observed in dogs among various species of domestic animals. Therefore, we attempted to assess sera from 221 livestock comprising cattle, sheep, goats, rabbits and horses, to identify the presence of TOSV neutralizing antibodies. The study was conducted during 2017, in 11 areas from the governorates of Blida, Medea, Algiers, Tipaza, Ain Defla, Tissemsilt in the north center, and Setif, Mila, Tizi Ouzou, Jijel in the northeast of Algeria. Positive results were obtained in 14.6% (12/82) cattle, 17.18% (11/64) sheep, 15% (3/20) horses and 3.33% (1/30) goats, whereas rabbits remained negative. Positive samples originated mainly from the north centre, with new areas being first-ever detected. The seroprevalence was noticed to be very strongly related to sample origin (p < 0.01). Females (OR=4.09) were observed to be more likely infected. Our findings represent a further proof of TOSV circulation in Algeria. Moreover, they revealed a potential role of livestock (p = 0.00731) in its natural cycle. This fact emphasize how important is to elucidate the exact contribution of livestock to the epidemiology of sandfly-borne phleboviruses, and their impact on public health.

Serological evidence of Rift Valley fever viral infection among camels imported into Southern Algeria.

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis caused by the Rift Valley fever virus (RVFV). The present work aims to investigate the epidemiological status and identify the risk factors associated with RVFV infection in dromedary camels (Camelus dromedarius) from southern Algeria. A total of 269 sera of apparently healthy camels was collected and tested using a competitive Enzyme-Linked Immunosorbent Assay (ELISA). Overall, 72 camels (26.7 %, 95 % CI: 21.4-32) were seropositive to RVFV. IgG antibodies were found to be most prevalent in camels from south-western areas, particularly in Tindouf wilaya (52.38 %, p < 0.0001), and in camels introduced from bordering Sahelian countries (35.8 %) (OR = 8.75, 95 %CI: 2.14-35.81). No anti-RVFV antibodies were detected in sera collected from local camels (0 %). Adult (5-10 years) and aged (>10 years) camels have a significantly higher risk of being infected by RVFV (OR = 2.15; 95 %CI = 1.21-3.81, OR = 2.05; 95 %CI = 1.03-4.11, respectively). This report indicated that dromedaries imported to the south-western areas are exposed to RVFV and may contribute to its spread in Algerian territories.

Cattle co-infection patterns by hemopathogens and their phylogenetic analysis during the tick season in Constantine and Mila, Northeast Algeria.

Tropical theileriosis, babesiosis, and anaplasmosis are the most dominant tick-borne infections in North Africa where they cause significant economic losses in ruminants' industry. The aim of the present work was to study infections and co-infection patterns in 66 cattle with clinical signs of piroplasmosis and/or anaplasmosis in two localities, Beni Hamidene and Grarem Gouga, districts of Constantine and Mila (Northeast of Algeria), respectively. This study was conducted between early May and late September during four years 2017, 2018, 2020, and 2021. PCR showed that the most frequent pathogen in cattle with clinical signs of piroplasmosis and/or anaplasmosis was Theileria annulata (66/66; 100%) followed by Babesia bovis (21/66; 31.8%), Anaplasma marginale (15/66; 22.7%), and Babesia bigemina (3/66; 4.5%) (p < 0.001). Giemsa-stained blood smears examinations revealed that 66.7% (44/66); 10.6% (7/66); and 9.1% (6/66) of cattle were infected by T. annulata, Babesia spp., and A. marginale, respectively (p < 0.001). PCR revealed seven co-infection patterns: T. annulata/A. marginale (15/66; 22.7%), T. annulata/B. bovis (21/66; 31.8%), T. annulata/B. bigemina (3/66; 4.5%), T. annulata/A. marginale/B. bovis (7/66; 10.6%), T. annulata/B. bovis/B. bigemina (2/66; 3%), T. annulata/A. marginale/B. bigemina (1/66; 1.5%), and T. annulata/A. marginale/B. bigemina/B. bovis (1/66; 1.5%). Phylogenetic analyses showed that T. annulata Tams1 and B. bigemina gp45 sequences were identical to isolates from Mauritania and South Africa, respectively. The three A. marginale amplicons obtained herein had 99.63 to 99.88% similarity between them. This study provides data that can be used to improve control programs targeting these cattle hemopathogens.

Francisella tularensis PCR detection in Cape hares (Lepus capensis) and wild rabbits (Oryctolagus cuniculus) in Algeria.

Tularemia is a zoonosis caused by the bacterium Francisella tularensis. Leporids are primary sources of human infections in the northern hemisphere. Africa is classically considered free of tularemia, but recent data indicate that this dogma might be wrong. We assessed the presence of this disease in wild leporids in Algeria. Between 2014 and 2018, we collected 74 leporids carcasses from spontaneously dead or hunted animals. Francisella tularensis DNA was detected by specific real-time PCR tests in 7/36 (19.44%) Cape hares (Lepus capensis) and 5/38 (13.15%) wild rabbits (Oryctolagus cuniculus). Known tularemia arthropod vectors infested half of the PCR-positive animals. At necropsy, F. tularensis-infected animals presented with an enlarged spleen (n = 12), enlarged adrenal glands (12), liver discoloration (12), hemorrhages (11), and pneumonia (11). Immunohistological examination of liver tissue from one animal was compatible with the presence of F. tularensis. Our study demonstrates the existence of tularemia in lagomorphs in Algeria. It should encourage investigations to detect this disease among the human population of this country.

MALDI-TOF MS Identification of Dromedary Camel Ticks and Detection of Associated Microorganisms, Southern Algeria.

This study used MALDI-TOF MS and molecular tools to identify tick species infesting camels from Tamanrasset in southern Algeria and to investigate their associated microorganisms. Ninety-one adult ticks were collected from nine camels and were morphologically identified as Hyalomma spp., Hyalomma dromedarii, Hyalomma excavatum, Hyalomma impeltatum and Hyalomma anatolicum. Next, the legs of all ticks were subjected to MALDI-TOF MS, and 88/91 specimens provided good-quality MS spectra. Our homemade MALDI-TOF MS arthropod spectra database was then updated with the new MS spectra of 14 specimens of molecularly confirmed species in this study. The spectra of the remaining tick specimens not included in the MS database were queried against the upgraded database. All 74 specimens were correctly identified by MALDI-TOF MS, with logarithmic score values ranging from 1.701 to 2.507, with median and mean values of 2.199 and 2.172 ± 0.169, respectively. One H. impeltatum and one H. dromedarii (2/91; 2.20%) tested positive by qPCR for Coxiella burnetii, the agent of Q fever. We also report the first detection of an Anaplasma sp. close to A. platys in H. dromedarii in Algeria and a potentially new Ehrlichia sp. in H. impeltatum.

Mosquito Vectors (Diptera: Culicidae) and Mosquito-Borne Diseases in North Africa.

Mosquitoes (Diptera: Culicidae) are of significant public health importance because of their ability to transmit major diseases to humans and animals, and are considered as the world's most deadly arthropods. In recent decades, climate change and globalization have promoted mosquito-borne diseases' (MBDs) geographic expansion to new areas, such as North African countries, where some of these MBDs were unusual or even unknown. In this review, we summarize the latest data on mosquito vector species distribution and MBDs affecting both human and animals in North Africa, in order to better understand the risks associated with the introduction of new invasive mosquito species such as Aedes albopictus. Currently, 26 mosquito species confirmed as pathogen vectors occur in North Africa, including Aedes (five species), Culex (eight species), Culiseta (one species) and Anopheles (12 species). These 26 species are involved in the circulation of seven MBDs in North Africa, including two parasitic infections (malaria and filariasis) and five viral infections (WNV, RVF, DENV, SINV and USUV). No bacterial diseases have been reported so far in this area. This review may guide research studies to fill the data gaps, as well as helping with developing effective vector surveillance and controlling strategies by concerned institutions in different involved countries, leading to cooperative and coordinate vector control measures.

First Isolation of Punique Virus from Sand Flies Collected in Northern Algeria.

In the last decade, several phleboviruses transmitted by sand flies were detected in the Mediterranean countries, with the health impact of some of them being unknown. From September to October 2020, a total of 3351 sand flies were captured in Kherrata (Bejaia, northern Algeria) and identified by sex, grouped in 62 pools, which were tested for the presence of phlebovirus RNA using endpoint RT-PCR. Two pools (male and female, respectively) were positive. The genome sequencing and phylogenetic analysis showed that the two phleboviruses detected were closely related to the Punique virus (PUNV) isolated in Tunisia and detected in Algeria. Both PUNV strains were isolated on VERO cells from positive pools. Morphological identification of 300 sand flies randomly selected, showed a clear dominance of Phlebotomus perniciosus (98.67%). The dominance of this species in the study area was confirmed by PCR targeting the mitochondrial DNA. Our result represents the first isolation of PUNV and the second report in Algeria from two distinct regions which confirm its large circulation in the country and more broadly in North Africa. Further studies are needed to measure the impact on public health through seroprevalence studies in humans as well as animals and to investigate its potential involvement in neurological viral diseases.

Presence of the sandfly-borne phlebovirus (Toscana virus) in different bio-geographical regions of Algeria demonstrated by a microneutralisation-based seroprevalence study in owned dogs.

Toscana virus (TOSV) is major meningitis and meningoencephalitis agent in the Mediterranean basin. Dogs are frequently exposed to TOSV; thereby they can contribute to estimating its circulation. In Algeria, little is known about its circulation, and available data are restricted to the Kabylian region. To investigate the current situation in Algeria, a total of 205 dog sera collected from 13 different wilayas over the country were analyzed by using in-house Enzyme Linked Immunosorbent Assay (ELISA) and microneutralization test (MNT). An overall seroprevalence rate of 20% (14.5-25.5%) was observed by ELISA. Whereas, a seroprevalence rate of 4.56% (1.65-7.43%) was recorded by microneutralization test elucidating the exact occurrence of TOSV exposure in dogs, in Algeria. Positive dogs were detected from the areas of Algiers, Bejaia, Blida, Bouira, Medea, Setif, and Tlemcen in the north; Laghouat in the high lands and Tamanrasset in great Sahara. Only one serum, originating from Bejaia in the north east, was positive for both testing methods, while 8/9 positive sera in MNT remained negative in ELISA. MNT negative/ELISA positive result of 40/41 might suggest evidence for dog transmission, and circulation of phleboviruses other than TOSV. Noticeably, TOSV and antigenically related viruses are largely prevalent. Thus, they are not only confined to Kabylia region, but are widespread in Algeria, despite its climate diversity.

Identification of Algerian field-caught mosquito vectors by MALDI-TOF MS.

Vector-borne diseases represent a real threats worldwide, in reason of the lack of vaccine and cure for some diseases. Among arthropod vectors, mosquitoes are described to be the most dangerous animal on earth, resulting in an estimated 725,000 deaths per year due to their borne diseases. Geographical position of Algeria makes this country a high risk area for emerging and re-emerging diseases, such as dengue coming from north (Europe) and malaria from south (Africa). To prevent these threats, rapid and continuous surveillance of mosquito vectors is essential. For this purpose we aimed in this study to create a mosquito vectors locale database using MALDI-TOF mass spectrometry technology for rapid identification of these arthropods. This methodology was validated by testing 211 mosquitoes, including four species (Aedes albopictus, Culex pipiens, Culex quinquefasciatus, and Culiseta longiareolata), in two northern wilayahs of Algeria (Algiers and Bejaia). Species determination by MALDI TOF MS was highly concordant with reference phenotypic and genetic methods. Using this MALDI-TOF MS tool will allow better surveillance of mosquito species able to transmit mosquito borne diseases in Algeria.

Mediterranean spotted fever and peripheral facial nerve palsy: a rare neurological complication.

Mediterranean spotted fever (MSF) caused by the bacterium Rickettsia conorii is one of the oldest known tick-borne diseases. It is transmitted by the brown dog tick Rhipicephalus sanguineus and occurs mainly in the Mediterranean area. MSF usually presents with a skin rash, high fever, and characteristic eschar at the site of the tick bite. The course of this disease may be benign or life-threatening. Focal neurological manifestations are unusual. We report the case of a patient who presented with an isolated peripheral facial nerve palsy complicating R conorii conorii infection.

Microorganisms associated with the North African hedgehog Atelerix algirus and its parasitizing arthropods in Algeria.

Hedgehogs are small mammals. They are potential reservoirs of various zoonotic agents. This study was conducted in Bouira, a north-central region of Algeria. A total of 21 Atelerix algirus corpses were picked up on roadsides and gardens. Hedgehog kidneys, spleens and ectoparasites were collected. Twelve hedgehogs were infested with ectoparasites, including Archaeopsylla erinacei, Rhipicephalus sanguineus s.l. and Haemaphysalis erinacei. Hedgehog organs and randomly selected arthropods were screened for microorganisms using molecular methods. Coxiella burnetii was detected in kidneys, spleens, A. erinacei, Hae. erinacei and Rh. sanguineus s.l. Leptospira interrogans was detected in kidneys. Rickettsia felis and Rickettsia massiliae were detected respectively in A. erinacei and in Rh. sanguineus s.l. DNA of an uncultivated Rickettsia spp. was found in Hae. erinacei. Wolbachia spp. DNA was detected in fleas. The DNA of potential new Bartonella and Ehrlichia species were found respectively in fleas and ticks. This study highlights the presence of DNA from a broad range of microorganisms in hedgehogs and their ectoparasites that may be responsible for zoonoses in Algeria.

Phlebotomine sandflies and associated pathogens in Algeria: update and comprehensive overview.

Being the only established vectors of the protozoan parasites of the genus Leishmania, sand flies have become very important in all countries where leishmaniasis exists. It is caused by a variety of species, each one having specific mammalian reservoir hosts and vectors. Leishmania and sand fly classification has always been a controversial matter, and the increasing number of sand fly species described world complicates the task. Until recently, sand flies distributed in the Old World were known as vectors for few Phleboviruses including two known species (Sandfly fever Naples virus, and alehebad virus), and tentative species such as sand fly fever Sicilian virus and Corfou virus. These infections are emerging in the Mediterranean region and will likely spread in forthcoming decades, posing a complex threat to public health. Here, we reviewed the current literature on phlebotomine sand flies fauna and epidemiology of sand fly­borne infections in Algeria.

Bacterial Infections in Humans and Nonhuman Primates from Africa: Expanding the Knowledge.

The close phylogenetic relationship between humans and other primates creates exceptionally high potential for pathogen exchange. The surveillance of pathogens in primates plays an important role in anticipating possible outbreaks. In this study, we conducted a molecular investigation of pathogenic bacteria in feces from African nonhuman primates (NHPs). We also investigated the pathogens shared by the human population and gorillas living in the same territory in the Republic of Congo. In total, 93% of NHPs (n=176) and 95% (n=38) of humans were found to carry at least one bacterium. Non-pallidum Treponema spp. (including T. succinifaciens, T. berlinense, and several potential new species) were recovered from stools of 70% of great apes, 88% of monkeys, and 79% of humans. Non-tuberculosis Mycobacterium spp. were also common in almost all NHP species as well as in humans. In addition, Acinetobacter spp., members of the primate gut microbiota, were mainly prevalent in human and gorilla. Pathogenic Leptospira spp. were highly present in humans (82%) and gorillas (66%) stool samples in Congo, but were absent in the other NHPs, therefore suggesting a possible gorillas-humans exchange. Particular attention will be necessary for enteropathogenic bacteria detected in humans such as Helicobacter pylori, Salmonella spp. (including S. typhi/paratyphi), Staphyloccocus aureus, and Tropheryma whipplei, some of which were also present in gorillas in the same territory (S. aureus and T. whipplei). This study enhances our knowledge of pathogenic bacteria that threaten African NHPs and humans by using a non-invasive sampling technique. Contact between humans and NHPs results in an exchange of pathogens. Ongoing surveillance, prevention, and treatment strategies alone will limit the spread of these infectious agents.

Infection by haemopathogens and tick infestation of sheep during summer season in Constantine region, Northeast Algeria.

A study on tick infestation of 43 sheep with clinical symptoms of piroplasmosis and anaplasmosis was carried out during summer seasons of 2016 and 2017 in 34 sheep flocks from Beni Hamidene locality, district of Constantine, Northeast Algeria. Only animals with clinical symptoms of piroplasmosis and/or anaplasmosis were checked for tick infestation. Among the 43 examined sheep, 58 ± 15% were infested by ticks. A total of 185 adult ticks (100 males and 85 females) were collected from the 25 sheep. Two tick genera, Rhipicephalus and Hyalomma consisting of four species were collected, Rhipicephalus bursa was the most frequent tick (164/185; 88.6 ± 4.6%), followed by Rhipicephalus sanguineus sensu lato (16/185; 8.6 ± 4%), Rhipicephalus (Boophilus) annulatus (4/185; 2.2 ± 2.1%) and Hyalomma scupense (1/185; 0.5 ± 1%). Mean overall tick infestation intensity was 7.4. Mixed infestations with two tick species were found in 10 sheep (23.3 ± 12.6%). All farmers (34/34) used ivermectin, and only 11% of them used acaricide to control ticks. The majority of R. bursa ticks (87/185; 45 ± 7%) were located on the ears 37/185; 20 ± 6%) and the testicles (50/185; 27 ± 6%). Giemsa-stained blood smears examination showed the presence of three haemopathogens: Anaplasma spp. (19/43; 44 ± 15%); Babesia spp. (6/43; 14 ± 10%) and Theileria spp. (1/43; 2 ± 4%). These results showed the presence of several low infestation burdens by ticks transmitting three haemopathogens.

Implementation of an in-house real-time reverse transcription-PCR assay for the rapid detection of the SARS-CoV-2 Marseille-4 variant.

INTRODUCTION: The SARS-CoV-2 pandemic has been associated with the occurrence since summer 2020 of several viral variants that overlapped or succeeded each other in time. Those of current concern harbor mutations within the spike receptor binding domain (RBD) that may be associated with viral escape to immune responses. In our geographical area a viral variant we named Marseille-4 harbors a S477 N substitution in this RBD. MATERIALS AND METHODS: We aimed to implement an in-house one-step real-time reverse transcription-PCR (qPCR) assay with a hydrolysis probe that specifically detects the SARS-CoV-2 Marseille-4 variant. RESULTS: All 6 cDNA samples from Marseille-4 variant strains identified in our institute by genome next-generation sequencing (NGS) tested positive using our Marseille-4 specific qPCR, whereas all 32 cDNA samples from other variants tested negative. In addition, 39/42 (93 %) respiratory samples identified by NGS as containing a Marseille-4 variant strain and 0/26 samples identified as containing non-Marseille-4 variant strains were positive. Finally, 2018/3960 (51%) patients SARS-CoV-2-diagnosed in our institute, 10/277 (3.6 %) respiratory samples collected in Algeria, and none of 207 respiratory samples collected in Senegal, Morocco, or Lebanon tested positive using our Marseille-4 specific qPCR. DISCUSSION: Our in-house qPCR system was found reliable to detect specifically the Marseille-4 variant and allowed estimating it is involved in about half of our SARS-CoV-2 diagnoses since December 2020. Such approach allows the real-time surveillance of SARS-CoV-2 variants, which is warranted to monitor and assess their epidemiological and clinical characterics based on comprehensive sets of data.

Cross-sectional survey of cattle haemopathogens in Constantine, Northeast Algeria.

This aim of the present study was to estimate the prevalence of haemopathogens in cattle in Beni Hamidene locality, district of Constantine (Νortheastern Algeria). Between June and October 2014, 169 bovines from 25 farms were included in this survey, 32 (18.9%) among them were suspected of piroplasmosis and/or anaplasmosis. Infection prevalences were estimated by microscopic examination of Giemsa-stained blood smears and blood samples from all included cattle (n = 169). Animals were infected by Theileria annulata (65/169; 38.46%), Anaplasma marginale (22/169; 13%) and Babesia bovis (5/169; 3%). Two co-infection patterns were found: Theileria annulata/Anaplasma marginale (7.69%) and Theileria annulata/Babesia bovis (1.18%). Only one farm had no cattle infected by any of the haemopathogens. There was a signification difference of T. annulata infection prevalence according to age category (p =.04). These results emphasised mainly the presence of bovine tropical theileriosis in northeastern, Beni Hamidene locality, province of Constantine, Algeria.

Knowledge, attitude and perception of bovine piroplasmosis by cattle owners in Constantine, North-East of Algeria, using participatory epidemiology.

Cattle piroplasmoses are tick-borne diseases, spread worldwide that cause significant economic losses. A participatory epidemiological study was conducted individually or in focus groups with 73 cattle owners in Beni Hamidene locality (district of Constantine, Algeria). The aim of this study was to study cattle owners' knowledge, attitude and perception on cattle piroplasmosis. Proportional piling technique was used to determinate most common cattle diseases, and to evaluate economic impact of diseases according to the interwieved farmers. Theileriosis (49/73; 67.1%) and babesiosis (44/73; 60.3%) were considered the most important bovine diseases. No zoonotic disease was cited by the interviewed cattle owners. According to the majority of cattle owners, theileriosis and babesiosis are deadly diseases (87.3 and 78.1%, respectively). All cattle owners (73/73) cited fever as the most common symptom of tropical theileriosis. Some of them (14/73; 19.2%) do not make distinction between theileriosis and babesiosis. According to cattle owners (65/73; 89.0%), the use of acaricide is the most appropriate tick control method. This study provides information about knowledge on bovine piroplasmoses in Algeria. These information could be considered when performing control programmes by both animal decision-makers and field veterinarians.

Introduction into the Marseille geographical area of a mild SARS-CoV-2 variant originating from sub-Saharan Africa: An investigational study.

BACKGROUND: In Marseille, France, the COVID-19 incidence evolved unusually with several successive epidemic phases. The second outbreak started in July, was associated with North Africa, and involved travelers and an outbreak on passenger ships. This suggested the involvement of a new viral variant. METHODS: We sequenced the genomes from 916 SARS-CoV-2 strains from COVID-19 patients in our institute. The patients' demographic and clinical features were compared according to the infecting viral variant. RESULTS: From June 26th to August 14th, we identified a new viral variant (Marseille-1). Based on genome sequences (n = 89) or specific qPCR (n = 53), 142 patients infected with this variant were detected. It is characterized by a combination of 10 mutations located in the nsp2, nsp3, nsp12, S, ORF3a, ORF8 and N/ORF14 genes. We identified Senegal and Gambia, where the virus had been transferred from China and Europe in February-April as the sources of the Marseille-1 variant, which then most likely reached Marseille through Maghreb when French borders reopened. In France, this variant apparently remained almost limited to Marseille. In addition, it was significantly associated with a milder disease compared to clade 20A ancestor strains, in univariate analysis. CONCLUSION: Our results demonstrate that SARS-CoV-2 can genetically diversify rapidly, its variants can diffuse internationally and cause successive outbreaks.

Potential of Artesunate in the treatment of visceral leishmaniasis in dogs naturally infected by Leishmania infantum: Efficacy evidence from a randomized field trial.

Leishmaniasis is among the world's most neglected diseases. Dogs are the main reservoirs/hosts of Leishmania infantum, causative agent of both canine and human visceral leishmaniosis. Canine leishmaniasis (CanL) represents a public health problem as one of the most prevalent zoonotic diseases worldwide. Current therapeutics present drawbacks; thus, there is a need for more effective, safer, and cheaper drugs. The aim of this study was to evaluate and to compare the efficacy of oral administration of artesunate or meglumine antimoniate/allopurinol in dogs with clinical leishmaniasis. Forty-two dogs with naturally occurring clinical leishmaniasis were included in this open-label, simple randomized positive-control clinical field trial with 6 months of follow-up. Dogs received meglumine antimoniate 100 mg/kg/day and allopurinol 30 mg/kg/day for 28 days (control group, n = 26) or artesunate 25 mg/kg/day for 6 days (test group, n = 16). The animals were evaluated for their clinical evolution, parasite load (by qPCR) and humoral response at different time points: 0, 30, 90, and 180 days after treatment. Data analyses showed a significant improvement in both groups in clinical scores, parasitemia and antibody titers after treatment. Compared to the control group, the artesunate group showed significantly lower clinical score (P = 0.0001), lower parasitemia (P = 0.0001) and antibody titers after 6 months of follow-up. Compared to baseline values, a rapid, significant reduction (P < 0.012) in antibody levels, 2.28- versus 3.04-fold for the control versus artesunate groups, respectively, was observed 30 days after treatment. Antibody levels continued to decrease further in the artesunate group, where 58% of cases became seronegative at the 6-month follow-up. All qPCR-positive dogs were negative after treatment with artesunate, while 14.3% remained positive with the appearance of two new cases in the control group. Artesunate was well tolerated, and no side effects were recorded. Treatment failures were similar in both groups with 27.27% (6/22), including 18.18% (4/22) mortality in the control group, versus 26.66% (4/15), including 13.33% (2/15) mortality in the artesunate group. This is the first report showing the potential of artesunate in the treatment of dogs with clinical leishmaniasis. Artesunate showed higher efficacy than the current first-line treatment for CanL without any adverse effects. It could be a good alternative chemotherapy for CanL, and may be considered for further studies in human leishmaniases. Further clinical trials are needed to confirm these findings, to determine if there are relapses after treatment and if dogs remain infective to sandflies, to define the ideal therapeutic dosage and duration of treatment with artesunate.

Tularemia as a Mosquito-Borne Disease.

Francisella tularensis (Ft) is the etiological agent of tularemia, a disease known for over 100 years in the northern hemisphere. Ft includes four subspecies, of which two are the etiologic agents of tularemia: Ft subsp. tularensis (Ftt) and Ft subsp. holarctica (Fth), mainly distributed in North America and the whole northern hemisphere, respectively. Several routes of human infection with these bacteria exist, notably through bites of Ixodidae ticks. However, mosquitoes represent the main vectors of Fth in Scandinavia, where large tularemia outbreaks have occurred, usually during the warm season. The mechanisms making mosquitoes vectors of Fth are still unclear. This review covers the inventory of research work and epidemiological data linking tularemia to mosquitoes in Scandinavia and highlights the gaps in understanding mosquitoes and Ft interactions.