Leishmania parasites are transmitted to humans and other mammals through the bites of phlebotomine sand flies, tiny insects belonging to the order Diptera and the family Psychodidae. Among the various Leishmania species, L. infantum is particularly consequential: it is the causative agent of both visceral leishmaniasis, the potentially fatal form of the disease that attacks internal organs, and cutaneous leishmaniasis, which produces disfiguring skin lesions. In the eastern Mediterranean basin, several sand fly species are known or suspected to transmit L. infantum, including Phlebotomus perfiliewi, Phlebotomus tobbi, and Phlebotomus neglectus. Yet the identity and relative importance of vector species vary considerably from one geographic area to another, and in many places the picture remains incomplete.

Israel presents a particularly complex epidemiological landscape. Multiple Leishmania species are endemic in the country, and L. infantum causes both visceral and cutaneous disease in humans, with dogs serving as the main reservoir of the parasite. Despite decades of surveillance, the precise sand fly vectors responsible for transmitting L. infantum in different regions of Israel have remained uncertain. Phlebotomus syriacus, a member of the subgenus Larroussius, has been a common species in the country and a long-standing suspect, but without molecular confirmation its actual role in the transmission cycle could only be speculated upon. Closing that gap was the central aim of the new study.

The research team, led by Liora Studentsky of the Hebrew University of Jerusalem and the Public Health Laboratories Jerusalem of the Israeli Ministry of Health, together with colleagues including corresponding author Oscar David Kirstein, conducted an intensive three-year field campaign between 2021 and 2023. Sand flies were collected using CDC miniature light traps at two villages where leishmaniasis is endemic: Aderet in central Israel and Kahal in the north. The choice of two ecologically distinct sites allowed the researchers to compare vector communities and infection patterns across different parts of the country, providing a more nuanced picture of the transmission system than a single-site study could offer.

The scale of the collection effort was substantial. In total, 20,634 sand flies were captured, of which 13,676, or 66.3 percent, were females, the sex responsible for blood feeding and therefore for parasite transmission. From this pool, the researchers analyzed 4,635 samples representing 5,050 individual female sand flies. Male specimens were identified by morphological examination, while females, which are harder to distinguish by morphology alone, were identified using molecular methods. In all, fourteen sand fly species were identified across the two sites, with species of the subgenus Larroussius dominating the catches at both locations.

The species composition differed markedly between the two villages, underscoring the heterogeneity of the transmission system. In Aderet, in central Israel, Phlebotomus syriacus was the prevalent species, accounting for 27.5 percent of the catch. In Kahal, in northern Israel, the community was structured differently: Phlebotomus galilaeus predominated at 54.1 percent, followed by Phlebotomus tobbi at 24.9 percent. This geographic variation in vector communities is epidemiologically significant because it means that different sand fly species may be responsible for maintaining transmission in different parts of the country, complicating any one-size-fits-all approach to vector control.

To detect the parasite, the researchers screened both unfed and blood-fed female sand flies using a technique known as real-time PCR with high-resolution melting analysis, or PCR-HRM, targeting the internal transcribed spacer 1 (ITS1) region of the parasite’s genome. This approach not only detects Leishmania DNA but also allows differentiation between Leishmania species based on the melting profiles of the amplified DNA. Three samples tested positive for L. infantum DNA: two individual unfed female Phlebotomus syriacus specimens collected in Aderet, and one pooled sample from Kahal. The detection in unfed females is particularly meaningful, since it reduces the likelihood that the DNA merely represented a recent, undigested blood meal from an infected host rather than a genuine infection of the fly itself.

These detections represent the first species-resolved identification of L. infantum DNA in Phlebotomus syriacus both in Israel and worldwide. While the finding stops short of proving that the species is a fully competent vector, since demonstrating vectorial capacity requires additional evidence such as the presence of infective parasite stages in the fly and experimental or epidemiological confirmation of transmission, it provides the first molecular evidence supporting Phlebotomus syriacus as a putative vector of L. infantum in central Israel. For a species that has been on the suspect list for years, this is a crucial step toward formal recognition of its role in the transmission cycle.

Blood-meal analysis added another important layer to the epidemiological picture. By sequencing the blood meals of engorged female sand flies, the researchers identified vertebrate hosts in 74.2 percent of the fed females examined. The results showed a strong dominance of cattle, which accounted for 84.8 percent of identified blood meals, followed by canids at 5.8 percent, with other mammals making up the remainder. The canid finding is especially relevant because dogs and other canids are the main reservoir hosts of L. infantum. Notably, Phlebotomus syriacus females were found to feed on canids in 16.7 percent of cases, a proportion that supports the species’ potential epidemiological relevance as a bridge between the animal reservoir and humans.

The combined findings paint a picture of a heterogeneous transmission system in which multiple sand fly species, different blood-feeding preferences, and geographically varying vector communities all interact to sustain L. infantum circulation. The authors conclude that these results have important implications for targeted surveillance and vector-focused control strategies. Rather than assuming a single vector species across the country, public health authorities may need to tailor monitoring and intervention efforts to the specific vector communities and reservoir dynamics of each region. The identification of cattle as the dominant blood-meal source also raises questions about the role of livestock in the ecology of the transmission system, whether as dead-end hosts that divert flies from reservoir animals or as contributors to sustaining large sand fly populations.

The study was supported by the public health laboratories of the Israeli Ministry of Health in Jerusalem, with fieldwork assistance from inspectors of the Israeli Ministry of Environmental Protection. The research was co-funded by the European Commission under grant 101057690 and by UKRI grants 10038150 and 10039289, as part of the CLIMOS project, one of six Horizon Europe initiatives forming the Climate Change and Health Cluster alongside BlueAdapt, CATALYSE, HIGH Horizons, IDAlert, and TRIGGER. This funding context reflects a growing recognition in Europe and beyond that climate change is altering the distribution and dynamics of vector-borne diseases, making detailed knowledge of local transmission systems increasingly urgent.

For Israel, the confirmation of L. infantum DNA in Phlebotomus syriacus fills a long-standing gap in the map of leishmaniasis transmission. For the broader eastern Mediterranean region, where Phlebotomus syriacus is also present, the finding suggests that this species may deserve closer attention in surveillance programs elsewhere as well. As the authors emphasize, understanding which sand fly species carry which Leishmania parasites, and under what ecological conditions, is fundamental to designing effective interventions, whether through insecticide spraying, reservoir dog management, or environmental modification. The first molecular evidence implicating Phlebotomus syriacus in L. infantum transmission marks a meaningful advance toward that goal, and it signals that the full complexity of leishmaniasis transmission in the region is only now beginning to come into focus.

Subject of Research: First molecular detection of Leishmania infantum DNA in the sand fly Phlebotomus syriacus and its implications for leishmaniasis transmission in Israel

Article Title: First detection of Leishmania infantum DNA in Phlebotomus (Larroussius) syriacus and its epidemiological implications in Israel

Article References: Studentsky, L., Kirstein, O. D., Diaz, D., Elbaz, S. L., Ben Avi, I., Shalan, R., Okla, H., Shilo, S., Kalmus, S., Davidovich-Cohen, M., Orshan, L., & Baneth, G. (2026). First detection of Leishmania infantum DNA in Phlebotomus (Larroussius) syriacus and its epidemiological implications in Israel. Parasites & Vectors. https://doi.org/10.1186/s13071-026-07623-7

Image Credits: AI Generated

DOI: 10.1186/s13071-026-07623-7

Keywords: Leishmania infantum, Phlebotomus syriacus, sand flies, leishmaniasis, vector-borne disease, PCR-HRM, blood meal analysis, Israel, visceral leishmaniasis, cutaneous leishmaniasis, Parasites & Vectors, vector surveillance

The study, conducted by an Ethiopian-led consortium including the Armauer Hansen Research Institute and international collaborators from the Drugs for Neglected Diseases initiative and Spain’s Instituto de Salud Carlos III, was a multicenter, randomized, controlled, open-label, adaptive Phase II/III trial. It compared a single session of thermotherapy, in which a heated device delivers 50 degrees Celsius to the lesion for 30 seconds, against the current standard of weekly injections of pentavalent sodium stibogluconate directly into the lesion, a regimen that must continue for four to six weeks. Participants were adults aged 18 to 60 years with parasitologically confirmed, uncomplicated localized cutaneous leishmaniasis, enrolled across Ethiopian treatment sites including ALERT Comprehensive Specialized Hospital, Boru Meda General Hospital, and Wacha Health Center.

The trial was designed with methodological rigor unusual for studies in this field. Prespecified futility and interim analyses guided progression through the trial phases, and an independent Data and Safety Monitoring Board oversaw the process, ultimately recommending that the final phase II analysis include 183 participants. Of these, 91 were randomized to thermotherapy and 92 to intralesional sodium stibogluconate. Most participants were men, 60.4 percent in the thermotherapy arm and 53.3 percent in the drug arm, and the median age was 27 years. Cure was assessed at two time points: initial cure evaluated at day 90 or 105, and final cure assessed at day 180, using both intention-to-treat and per-protocol analyses to capture different views of treatment effect.

The intention-to-treat results, which include every participant as randomized, showed that initial cure rates were 44.0 percent for thermotherapy and 52.2 percent for intralesional sodium stibogluconate, a difference that did not reach statistical significance (p = 0.266). Final cure rates at day 180 were similarly comparable in this analysis, at 34.1 percent versus 43.5 percent (p = 0.191). By contrast, the per-protocol analysis, restricted to participants who completed treatment as assigned, found a statistically significant advantage for the drug regimen, with final cure rates of 39.2 percent for thermotherapy versus 57.6 percent for intralesional sodium stibogluconate (p = 0.032). This divergence between analytic perspectives reflects an important practical reality: some participants in the drug arm did not complete the full multi-week injection course, whereas thermotherapy required only a single visit.

The safety findings were unambiguous. No serious adverse events were reported in either arm, and all observed adverse events were mild and resolved without complications. Health-related quality of life, measured with validated dermatological instruments, improved significantly in both treatment arms after cure, indicating that successful lesion healing translates into tangible benefits in patients’ daily lives regardless of which therapy achieved it.

From a technical standpoint, the trial’s design choices deserve attention. The thermotherapy protocol, a single application of 50 degrees Celsius for 30 seconds, exploits the thermal sensitivity of Leishmania parasites within skin lesions, inducing local parasite killing while sparing surrounding tissue. Intralesional sodium stibogluconate, by contrast, relies on pentavalent antimonial compounds delivered directly into the lesion over repeated weekly visits. The adherence advantage observed for thermotherapy is therefore not a minor convenience but a structurally meaningful difference: a treatment requiring one healthcare visit is far easier to complete than one demanding four to six weekly presentations, particularly for patients in rural Ethiopia who may travel long distances and bear significant opportunity costs for each clinic visit.

The authors argue that in resource-limited Ethiopian settings, where most cutaneous leishmaniasis cases go entirely untreated and patients risk lifelong disfigurement, thermotherapy provides a pragmatic, single-session alternative wherever access to intralesional sodium stibogluconate is constrained. The intention-to-treat equivalence, combined with superior adherence and an acceptable safety profile, supports this position, even as the per-protocol results caution that patients who can reliably complete the full drug course may achieve somewhat higher cure rates with the standard therapy. The nuance matters for policy: the best treatment is not only the most efficacious in ideal conditions but the one patients can actually finish.

The study also fills a glaring evidence gap. Ethiopian clinical practice for L. aethiopica infections has historically been informed by trials conducted in other regions with different parasite species, most commonly Leishmania major or Leishmania tropica, whose responses to heat and antimonials can differ. By generating species-specific, locally grounded data, the trial gives Ethiopian clinicians and national program managers the kind of evidence needed to tailor treatment guidelines to the parasite actually circulating in their highland foci.

Funding for the work came in part from the European and Developing Countries Clinical Trials Partnership (EDCTP2) programme supported by the European Union, with the study device and medications supplied by the Drugs for Neglected Diseases initiative and molecular work supported by the Armauer Hansen Research Institute and Instituto de Salud Carlos III. The trial was registered in the Pan African Clinical Trials Registry (PACTR202205775486864) on 30 May 2022, and the article was published open access in BMC Medicine on 19 September 2026, ensuring that the results are freely available to the health systems that most need them.

For the global community working on neglected tropical diseases, the trial’s message is twofold. First, heat-based therapy can credibly compete with injectable drug regimens for localized cutaneous leishmaniasis when adherence to prolonged treatment is unrealistic, making it a candidate for scale-up in endemic districts. Second, the divergence between intention-to-treat and per-protocol outcomes is a reminder that in real-world neglected disease care, the route and duration of treatment are as decisive as the drug itself. As Ethiopia and neighboring endemic countries weigh how to expand care for a disease that has long hidden in plain sight, a thirty-second burst of controlled heat, delivered in a single visit, may prove to be one of the most pragmatic tools at their disposal.

Subject of Research: A phase II randomized controlled trial comparing thermotherapy with intralesional sodium stibogluconate for Leishmania aethiopica cutaneous leishmaniasis in Ethiopia

Article Title: Thermotherapy compared with intralesional sodium stibogluconate for Leishmania aethiopica cutaneous Leishmaniasis in Ethiopia: A phase II randomized controlled trial

Article References: Thermotherapy compared with intralesional sodium stibogluconate for Leishmania aethiopica cutaneous Leishmaniasis in Ethiopia: A phase II randomized controlled trial. (n.d.). https://doi.org/10.1186/s12916-026-05244-6

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05244-6

Keywords: cutaneous leishmaniasis, Leishmania aethiopica, thermotherapy, intralesional sodium stibogluconate, randomized controlled trial, Ethiopia, treatment efficacy, neglected tropical diseases, phase II trial, adherence, BMC Medicine, public health