Derya Alabaz1, Fadime Eroğlu2, Hüseyin Elçi3 and Ümmühan Çay1.
Department of Pediatrics, Pediatric Infectious Diseases, Faculty of Medicine, Cukurova University, Adana, Turkey.
2 Aksaray University, Basic Sciences Medical Parasitology Departman, Aksaray, Turkey.
3 Department of Pediatrics, Kızıltepe State Hospital, Kızıltepe, Mardin.
Derya ALABAZ Mailing address: Cukurova University, The Faculty of
Medicine, Pediatric Infection Department Adana, Turkey. Tel:
05326534166. E-mail: email@example.com
Published: July 1, 2022
Received: March 1, 2022
Accepted: June 16, 2022
Mediterr J Hematol Infect Dis 2022, 14(1): e2022053 DOI 10.4084/MJHID.2022.053
| This is an Open Access article distributed
under the terms of the Creative Commons Attribution License
which permits unrestricted use, distribution, and reproduction in any
medium, provided the original work is properly cited.
Background and Objective: Protozoa of the genus Leishmania are obligate intracellular parasites, and Leishmania
species cause a spectrum of species-specific clinical symptoms known as
cutaneous, mucocutaneous, and visceral leishmaniasis. For example, Leishmania major and Leishmania tropica cause cutaneous leishmaniasis, while Leishmania infantum and Leishmania donovani
cause visceral leishmaniasis (VL). However, molecular studies in recent
years have shown that Leishmania species cause different clinical
Our aim was to evaluate the relationship between the clinical and
molecular characterization of leishmania isolates in children with VL
defined in Turkey, an intercontinental transitional region.
The clinical diagnosis of VL was confirmed by detecting amastigotes in
the bone marrow aspirate and/or the rK39 test and/or molecular methods
(genus-specific PCR, Real-Time PCR, ITS1 PCR-RFLP, DNA sequencing).
Most of the VL patients were referred from the districts of Adana
(53.3%) and others from neighboring provinces; Hatay (16.6%), Osmaniye
(3%), Gaziantep (3%), Adıyaman (3%), and 20% case were Syrian
immigrants A clinical diagnosis of VL was confirmed in 30 patients with
different diagnostic methods. 93% was found positive with microscopic
examination, 79.1% with rK39 dipstick test, and 60% with genus-specific
PCR assay in clinical samples. The Leishmania isolates were identified as L. infantum (40%), L. donovani (26.7%), and L. tropica
(23.3%) using Real-Time PCR, ITS1 PCR-RFLP, and DNA sequencing. There
was no cutaneous finding in any case in clinical examination.
most common clinical findings were fever (93.3%) and splenomegaly
(90%), followed by hepatomegaly (76.6%). The most common laboratory
finding was thrombocytopenia (86.6%), followed by anemia (70%). In
addition, hemophagocytic lymphohistiocytosis was detected in bone
marrow aspiration in two of our patients. Since pentavalent antimony
salts treatment initially failed in four patients, it was necessary to
switch to Liposomal-Amphotericin B with treatment success.
Conclusions: The presence of L. tropica
in VL patients, despite the absence of cutaneous findings in any of the
cases, shows that this strain can cause VL, contrary to conventional
knowledge. In the Adana province, where this study was carried out, L. infantum
from CL cases in previous studies should be taken into account, and
visceral spread in CL cases and accompanying cutaneous lesions in VL
cases should be investigated in detail.
Leishmaniasis, a chronic and persistent intracellular protozoal infection caused by many different species in the genus Leishmania,
according to the World Health Organization (WHO), is one of the most
neglected tropical diseases in the world. It is a poverty-associated
parasitic disease that is endemic in over 90 countries and transmitted
by sandflies and is associated with malnutrition, displacement,
inadequate housing, illiteracy, weakened immune systems, and lack of
resources. Leishmaniasis is also related to geographic changes, and the
geographic distribution of leishmaniasis cases reflects the mobility of
the population in displacement.
There are three main forms of
the disease: Cutaneous leishmaniasis (CL), Visceral leishmaniasis (VL),
also known as kala-azar (KA), and Mucocutaneous leishmaniasis
(MCL).[3,4] It is known that approximately twenty Leishmania species are the causative agents of leishmaniasis, of which Leishmania tropica (L. tropica) is the causative agent of CL, while Leishmania donovani (L. donovani) and Leishmania infantum (L. infantum)
are the causative agents of VL in the literature to date. However, in
molecular studies on Leishmania species in recent years, it has been
reported that L. donovani and L. infantum can
also cause CL in some cases.[5,6,7] Global warming and changes in
climatic conditions may affect the distribution of the causative
species of this disease. In addition, the molecular epidemiology of
leishmaniasis may change with the increase in migration due to war in
regions where leishmaniasis is endemic and the rise in business and
touristic travels with the developing technology. Therefore, up-to-date
information on this disease's molecular epidemiology is needed in
regions where leishmaniasis is endemic. The aim of this study was to
identify the causative Leishmania species in children with a clinical diagnosis of VL and to investigate the effects of these species on the disease.
Materials and Methods
Study Area and Clinical Analysis.
Turkey is located at 36° to 42° North latitude and is described as one
of the endemic countries for leishmaniasis. Turkey is divided into
seven regions covering a surface area of 783.562 km2.
Adana province, where the study was conducted, is located at 37° north
latitude and 35.32° east longitude in the eastern Mediterranean region.
Adana province borders Osmaniye, Kahramanmaras, Gaziantep in the east,
Icel in the west, Nigde in the northwest, Hatay in the southeast, the
Mediterranean Sea in the south, and Syria in the southeast. Due to its
location, Adana province receives a lot of immigration, especially from
Syria. In addition, the Adana has the characteristics of the
Mediterranean climate, the median relative humidity is approximately
90%, and the median temperature is 28°C. The geographical and climatic
conditions of Adana province are suitable for the development of Phlebotomus species, which are the causative agents of leishmaniasis.
study characterizes pediatric patients admitted for investigation and
confirmed diagnosis of VL by Çukurova University Hospital, Pediatric
Infectious Diseases Department, Adana, in the south of Turkey. It
serves as a research hospital and is an important center where patients
come for treatment from the south/southeast regions of Turkey and
Syrian immigrants. In addition, other family members of the case were
questioned and examined in terms of clinical findings, and simple
hematological tests were performed.
In the clinical examination of
the patients included in this study, permanent systemic infections such
as fever, fatigue, anorexia, weight loss, and sizes of liver and spleen
were investigated. In addition, demographic characteristics of the
patients, such as age and gender, were examined in this study. Body
mass index (BMI) was determined by dividing weight (kg) by height (m)
squared. On WHO charts, the normal range is generally defined as
between -2 SD and +2 SD (i.e., Z-scores between -2.0 and +2.0),
corresponding to approximately the 2nd and 98th percentiles. In
addition, non-specific laboratory data such as full blood count,
gamma-globulin concentration, and erythrocyte sedimentation rate (ESR)
Clinical examination of VL was confirmed by detection of amastigotes in
bone-marrow aspirate, and/or rK39, and/or molecular tests
(genus-specific PCR, Real-Time PCR, ITS1 PCR-RFLP, DNA sequencing, and
The bone marrow sample was smeared onto a glass slide. The prepared
bone marrow samples were fixed with absolute methanol, stained with 10%
Giemsa, and examined under the light microscope with magnification oil
100X objective. The preparations with amastigote were considered
positive, and those without amastigote were considered negative.
The Recombinant Antigen Dipstick Test (rK39).
The rapid immune-chromatographic test is based on a recombinant
39-amino acid repeat antigen. The dipstick test was performed according
to the manufacturers' instructions (InBios International, Inc. Seattle,
WA). Twenty microliters of serum taken from the patients were mixed
with two drops of buffer in the rK39 dipstick test. After 10 minutes of
incubation, serum samples with two bands on the cellulose strip were
considered positive, and serum samples without were considered negative
only if the control band appeared.
Genus-Specific PCR Assay.
DNA was extracted from bone marrow samples with an Agencourt DNA kit
(Beckman Coulter, Beverly, USA), according to the manufacturer's
protocol. The kDNA using the primers 13A (5'-GTG GGG GAG GGG CGT
TCT-3') and 13B (5'-ATT TTC CAC CAA CCC CCA GTT-3') was investigated
for the presence of Leishmania in clinical samples.. A reaction mix
with a final volume of 25 µL consisted of 0.2 mM of dNTP, 1.5 mM MgCl2,
1 unit of Taq polymerase, 1 µM of each primer, and 5 µL DNA samples for
use PCR analyses. The DNA was amplified for 35 cycles in a
thermocycler, set to run at 94°C for 1 min, 54°C for 1 min, and 72°C
for 1 min for each one.
The amplification reactions were
analyzed by bromide staining and visualization under UV light. The PCR
products with a fragment image of approximately 120 bp under UV light
were considered positive.
Real-Time PCR Assay. The kDNA minicircle gene region was targeted to identify Leishmania
species, and Leishmania isolates were amplified by melting real-time
curve PCR (Real-Time PCR) using primers JW13 and JW14. The Real-Time
PCR was performed by hot-start PCR using the LightCycler FastStart DNA
Master SYBR Green I Kit in a LightCycler™ (Roche Diagnostics). The 20
µL reaction mixture contained 1 X LightCycler FastStart DNA Master SYBR
Green I (Roche Diagnostics, Meylan, France), 2 mM MgCl2, 10 µM of each primer and 5 µL of DNA of the parasite.
Real-Time PCR Reaction and DNA samples were amplified using a 35 cycles
thermal cycler program consisting of 10 s at 95°C, 10 s at 53°C, and 10
s at 72°C. The melting program consisted of one cycle of 95°C for 10 s,
67°C for 10 s, and heating at 0.1°C per 1 second to 98°C. The
transition rates were 20°C/s except for the extension step and the
final step, which had a temperature transition rate of 1°C/s and 0.1°C,
respectively. Fluorescence was measured through the slow heating phase.
For improved visualization of the melting temperatures (Tm), melting
peaks were derived from the initial melting curves (fluorescence [F] versus temperature [T]
by plotting the negative derivative of fluorescence over-temperature
–dF/dT versus dT). The melting temperatures were 88.5±0.4°C for L. donovani, 89.3±0.2°C for L. tropica, and 90.5±0.2°C for L. infantum, respectively.
ITS1 PCR-RFLP Assay.
In this study, to identify Leishmania species according to the study of
Schönian et al., the ITS1 gene region was targeted, and LITSR-L5.8S
primers were designed. The 40 µL PCR reaction mixture consisted of
PCR buffer 1 X (75 mM KCl, pH 8.3 and 20 mM Tris-HCl, 1.5 mM MgCl2,
1U Taq polymerase), 0.2 mM dNTPs, 0.5 pmol of each primer and 5 µL of
DNA sample. After the initial denaturation (5 min at 94°C), 35 cycles
of denaturation for 1 min at 94°C, annealing for 1 min at 54°C, and
elongation for 1 min at 72°C were carried out, and a final extension
terminated the PCR at 72°C for 10 min. The PCR products were analyzed
in 1% agarose gel by electrophoresis at 100 V in 1 X Tris-boric-EDTA
buffer (0.04 mM Tris-boric and 1mM EDTA, pH 8) and visualized by UV
light after being stained with ethidium bromide.
All PCR samples
with approximately 350 bp fragment length bands were considered
positive according to the agarose gel electrophoresis. ITS1 PCR
products (10 µL) were digested with the Hae III restriction enzyme
(Promega, Wisconsin, USA) according to the manufacturer's instructions,
and the restriction fragments were analyzed by 2% agarose gel
electrophoresis. The restriction products were identified as L. donovani, L. infantum, and L. tropica, according to Schönian et al.
ITS1 PCR products were purified for DNA sequencing using a SentroPure
DNA purification kit (Sentromer DNA, Istanbul, Turkey). Purified PCR
products were sequenced with LITSR-L5.8S primers using BigDye
Terminator V 3.1 cycle sequencing kit (Applied Biosystems). This
reaction was analyzed according to the instructions for the 3730 DNA
analyzer (Applied Biosystems). The ITS1 PCR products of Leishmania isolate sequences were approximately 320 bp in length. The reference strains of Leishmania species (L. donovani ATC 50212, WHOM/IN/80/DD8; L. infantum ATCC 501340, WHOM/TN/80/IPT-1; L. tropica
ATCC 50129, WHOM/SU/74/K27) were used in this analysis. The obtained
sequences were processed with the available GenBank and checked using
basic local alignment search tool (BLAST) analysis software (www.ncbi.nlm.nih.gov/BLAST).
The conventional treatment of VL/kala-azar consists of pentavalent
antimony salts (PAS- Sbv) - sodium stibogluconate (SSG (Pentostam)) and
meglumine antimoniate (MA, (Glucantime®)). In addition, liposomal
amphotericin B (L-AMB (AmBisome®)) was used intravenously at a dosage
of 3 mg/kg on days 1-5, 10, and 21 (for a cumulative dose of 21 mg/kg).
The therapy used in our department was one of the following in Table 1 (choice made according to a supplied drug that day, and/or the patient's suitability, and/or the physician's preference).
||Table 1. Used antileishmanial drugs in this study and their prescribed dosage.
Post-treatment follow-up (at least 1 year, every month for the first 3
months, then every 2 months, and every 3 months after 6 months)
included clinical examination, blood cell count, and ESR.
The medications used and/or management modalities were collected on a
spreadsheet. The Statistical Package for the Social Sciences (SPSS)
version 23.0 (IBM, Somers, NY, USA) was used for statistical analysis.
Categorical measurements were summarized as numbers and percentages,
while continuous measurements were summarized as mean, deviation, and
Confidentiality and patient privacy were maintained throughout the
process. Ethical approval was obtained from Çukurova University
Scientific Research Ethics Committee (decision no: 03.04.2022/120) and
was performed in accordance with the ethical standards of the
Declaration of Helsinki.
this study, the VL clinical diagnosis of 30 patients was confirmed by
different diagnostic methods. According to the results of microscopic
examination, 28 (93%) of 30 patients who were clinically diagnosed with
VL were found to be positive, while 2 patients (7%) were negative. Of
the patients with VL, 19 (79.1%) were positive, and 5 (20.9%) were
negative using the rK39 dipstick test. However, the rK39 dipstick test
could not be studied in 6 (20%) patients for technical reasons. The
leishmania parasite was detected by genus-specific PCR assay in 27
(90%) VL patients. Still, genus-specific PCR assay could not be studied
in 3 (10%) of the VL patients due to technical reasons in the
laboratory. The Real-Time PCR method was used to identify Leishmania species in VL patients, and 12 (40%) L. infantum, 8 (26.7%) L. donovani, and 7 (23.3%) L. tropica
were identified in the study; according to this method. ITS1 PCR-RFLP
assay and DNA sequencing were analyzed to confirm the Leishmania
species in this study. The results of the ITS1 PCR-RFLP assay confirmed
the Real-Time PCR results in this study. In addition, each of the
samples and reference strains of Leishmania species (L. donovani ATC 50212, WHOM/IN/80/DD8; L. infantum ATCC 501340, WHOM/TN/80/IPT-1; L. tropica ATCC 50129, WHOM/SU/74/K27) was identical to the sequence of Leishmania
species reported in GenBank. Compared with the previous records in
GenBank, we determined 100% similarity between sequences of leishmania
isolates from VL patients and Leishmania strains in GenBank. All of the diagnostic results used in this study have been shown in Table 2 and Figure 1.
The Leishmania species and the patients' clinical symptoms were
compared, and no significant relationship was found between them.
In addition, the epidemiological findings, clinical features, treatment, and outcome of the patients with VL have been shown in Table 2.
Most of the VL patients were referred from the districts of Adana
(53.3%) and others from neighboring provinces; Hatay (16.6%), Osmaniye
(3%), Gaziantep (3%), Adıyaman (3%), and 20% case were Syrian
immigrants (Table 3). Therefore, it was determined that 76.6% of the patients in this study lived in rural areas, and 23.4% lived in urban areas.
||Table 2. Demographic findings of the patients diagnosed VL.
||Figure 1. Venn diagram
with data about PCR, r K39 and microscopic examination positivity
regarding VL patients (N: 30 VL pediatric case).
||Table 3. Distribution of Leishmania strains by age and provinces.
to family history, a sibling of Case 3 was previously diagnosed with
VL, while the father of Case 11 had just died due to VL before the boy
applied. The median age of the 30 patients [20 male (66.7%)] was 37
months (range 12 months – 12 years, mean ± SD, 47.96 ± 32.87 months).
of symptoms before admission ranged from 3 days to 6 months (mean 37.5
± 46.3, median 20 days), while a Syrian boy (Case 23) complained for 3
years of abdominal distention and pallor. In the study, the body mass
index values of the patients were 14,9 (12,1-21,15) on average, and
malnutrition was detected in 34.48 % of our patients (Figure 2);
10 cases were below the BMI -2 score. No association was found between
BMI and parasite type. Fever was present in all patients except 2
(93.3%) (Table 3). The duration
of fever persists between 3 and 21 days (mean 10.9± 5.3, median 10
days) after beginning treatment. In the study, splenomegaly (90%) and
hepatomegaly (76.6%) were found to be the most common clinical findings
after fever (93.3%). No relationship was found between symptoms and
parasite types. The most common laboratory finding was thrombocytopenia
(86.6%), followed by anemia (70%) (Table 4).
In two of our patients, we detected hemophagocytic lymphohistiocytosis
(HLH) in bone marrow aspiration (Case 18 and Case 2). HIV was not
detected in any patient. In this study, although the PAS regimens were
effective in the treatment, some disadvantages were experienced like
prolonged hospitalizations and side effects, such as malaise,
arthralgia, abdominal pain, increased levels of liver transaminases,
amylase, and lipase, vomiting, renal effects, and T-wave changes in the
||Distribution of patients according to body mass index. SDS = standard deviation scores.
||Table 4. Clinical findings of the VL diagnosed pediatric patients.
treatment outcome of only one of our patients remained unknown. This
patient was the child of a Syrian immigrant family, and they had
returned to their hometown; the patient's family discharged the patient
before the treatment was finished. Therefore, the patient's treatment
outcome could not be followed up. In this study, it was observed that 5
(17%) of VL patients did not respond to the initial PAS treatment. One
of these had anorexia, and the VL infection recurred. While four
unresponsive patients were shifted to L-AMB treatment, and a full cure
was achieved. Finally, a single patient who did not respond while
receiving L-AMB treatment was moved to PAS treatment, which was
concluded successfully (Table 2). No patient died.
to WHO data, more than 1 billion people live in leishmaniasis endemic
areas and are at risk for this disease. More than 90% of new cases
reported to WHO occurred in 10 countries: Brazil, China, Ethiopia,
Eritrea, India, Kenya, Somalia, South Sudan, Sudan, and Yemen.
Leishmania is also widespread in most countries in the Mediterranean
basin, including Turkey and our neighbor countries, Syria, Iran, and
Iraq. Turkey is an endemic area for CL, according to the data of
WHO. New outbreaks of CL cases in the southeast of Turkey are
concurrent with the start of the war in Syria (now a day, one of the
top countries in the world for CL) and large migration to Turkey;
in addition, Turkey is a geographical transition region that receives
immigrants from many other countries (e.g., Afghanistan, Pakistan).
Besides this, many people go to endemic areas outside of Turkey for
work and military duty (e.g., Iraq, Syria, Afghanistan). Leishmaniasis
is an important public health problem for Turkey due to its
geographical location, climatic conditions, and internal and external
It is emphasized that the development of infection with Leishmania
is a complex structure under the influence of different factors.
Individual factors (age group, nutritional status) and infecting
parasite species/virulence factors, as well as the host's immune
status, play a major role in the disease formation of this agent.
Macrophages and neutrophils are the primary cells interacting with Leishmania
parasites after host infection. Macrophages and neutrophils are
considered the primary cells that react to Leishmania infection. Still,
several other immune cells, such as monocytes, dendritic cells (DCs),
natural killer (NK) cells, and CD4+ and CD8+ T cells, as well as
effector molecules, such as cytokines like interferon (IFN)-γ and
interleukin (IL)-12 and nitric oxide (NO) produced by inducible NO
synthase (iNOS), play distinct roles in the host response. The
development of an immune response against Leishmania is associated with
the parasite's activation of CD4+ T cells and the differentiation of
these cells into T-helper (Th) 1 or Th2 effector cells. In addition,
interleukin 10 (IL-10) and transforming growth factor-beta (TGF-β),
which are defined as immune response regulators, play a key role in VL
formation by inducing parasite proliferation.[13,14]
prevalence of leishmaniasis is increasing rapidly in the pediatric
population in many parts of the world. The mechanisms underlying its
higher incidence in children still contain many speculations, and the
exact mechanism that causes VL sensitivity is unknown. Still, it is
thought to be associated with immunodeficiency in particular. In
addition, studies in South America and Africa have reported
malnutrition may increase the risk of VL infection in children.
Kumar et al. have examined the effect of malnutrition on the profile of
innate immune functions of polymorphonuclear neutrophil granulocytes
(PMNs) and monocytes by comparing well-nourished and malnourished
Indian patients with VL. They have reported that malnourished VL
patients were observed with severely dysfunctional PMNs and monocytes
in terms of ROS activity that could not be recovered by stimulation
with Leishmania parasites. Other studies have been conducted on the
relationship between malnutrition and VL infection and have suggested
that in many cases, malnutrition plays a critical role in the
progression of VL to its severe form.[16,17] In our study, malnutrition
was detected in 34.48% of patients, and VL infection recurred in a
patient during anorexia.
The clinical presentation, combined
with the epidemiological context and non-specific biological
parameters, raises suspicion of VL, but laboratory confirmation of
the diagnosis before deciding on treatment is required. The gold
standard for VL diagnosis is direct Leishmania amastigotes
visualization by microscopic examination in the Giemsa-stained slides
of tissue aspirate samples (spleen, bone marrow, or lymph node).
Although our success in the direct microscopic evaluation of the bone
marrow in the diagnosis was high (93.3%), two children were diagnosed
only by molecular testing, and these results made us think that many
cases may have been missed. The rK39 dipstick test positivity in the
current study was 79.1% in all VL patients. The PCR assays are a rapid
tool with high sensitivity (99%), allowing species-specific diagnosis,
therapeutic approach, and clinical progress.
shows that L. tropica is the causative agent of CL, while L. donovani
and L. infantum are the causative agents of VL. However, it has been
reported with the development of molecular methods that leishmaniasis
causative species vary. Recent studies have reported the presence of L. infantum in CL cases without a VL history and that of L. tropica in VL cases without a CL history.[21,22] The L. infantum, L. major, L. tropica, and L. donovani
from leishmaniasis agents have been reported in the southern/southeast
Anatolia region of Turkey.[23,24] In the present study, as causative
agents of VL in pediatric cases, L. infantum, L. donovani,
and L. tropica were as follows; 40%, 26.7%, and 23.3%, respectively. In the Persian Gulf War (1990-1991), L. tropica
was the causative agent for leishmaniasis in American soldiers and
veterans at bases in Bahrain and Northern Saudi Arabia,[6,25] and
several other reports from various parts of the world suggest that L. tropica
can cause VL.[26-28] Southern and southeast Anatolia has a geography
similar to the settlements where these notifications are made. In our
study, L. tropica was
isolated in VL patients without CL symptoms. Therefore, L. tropica may
be the causative agent for VL more than expected in the area of Turkey.
L. donovani and L. infantum
species have also been detected in VL patients. When the relationship
between Leishmania species and clinical symptoms was compared, no
significant association was found between them.
The VL is the
most severe form of leishmaniasis and represents a spectrum of chronic
infections. The incubation period ranges from weeks to months (even
years); thus, due to slow progression, most patients remain subclinical
and are correctly diagnosed only very late in the course of the
disease. While WHO estimates that the illness in Syria is 2-5 times
higher than the actual reported figures, this is frightening
considering the risk posed by asymptomatic Leishmania carriers to the
Turkish population, especially due to the massive influx of immigrants
from Syria in recent years. Due to the prolonged presence of
asymptomatic and subclinical people in the community, the VL infection
can be transmitted to many people. In addition, the asymptomatic VL
patients may serve as a silent reservoir of parasites, presenting a
risk to public health through infection of the phlebotomine vector.
Although most of our patients in our study had a history of being in
rural areas and having contact with sandflies, some lived in the city
and whose risks were not defined.
WHO has established a useful
and suspicious clinical case definition for a diagnostic algorithm:
being in an endemic area, prolonged fever (more than two weeks),
splenomegaly (mostly), and weight loss, also with pancytopenia, VL is
suspected in any case. Including VL in the differential diagnosis of
leukemia-like syndromes in infants living in/traveling (even in the
past) to endemic areas such as the Mediterranean basin. VL is an
infection not commonly managed by Turkish practitioners and even more
by the European physicians of Mediterranean and non-Mediterranean
countries, where immigrants can bring the disease. This situation can
lead to delayed recognition of undiagnosed reactivated VL,
inappropriate treatment in VL, and poor clinical outcomes.
is an endemic country for CL, with the main causative agent as L.
tropica. Although about a quarter of our VL cases, the cause was L.
tropica, cutaneous lesions were not found in any of them. Concomitant
cutaneous lesions should be investigated, and each patient with
cutaneous lesions should be examined in detail regarding visceral
spread. In southeast Anatolia, where CL is known to be endemic, the
possibility of VL in a patient diagnosed with leukemia should not be
Few anti-leishmanial formulas have been proven
worthy; PAS, L-AMB, pentamidine, miltefosine, and paromomycin.
Socio-economic and pharmaceutical conditions (production, distribution)
have a tremendous impact on the choice of therapeutic option.
Although only PAS is given free of charge by the government in Turkey,
L-AMB has recently become the first choice drug instead of PAS due to
its faster effect (7 days' hospitalization versus 28-30 days.
Approximately 17% of the patients were reported to fail to respond to
the current study's initial therapy; four failed to respond to PAS
therapy, resulting in a complete cure with L-AMB. Considering the cost
advantage of shortening the hospital stay, despite the high cost of
L-AMB treatment, it seems to be a cost-effective regimen compared to
antimonial agents with its high success rate and being the most
effective treatment.[34,35] In addition, the less toxic effect of L-AMB
confirms its preference.
The present study reveals that all three isolate L. infantum, L. donovani and L. tropica
are causative agents of pediatric VL in Turkey's south/southeast
Mediterranean region. However, this study must be supported by studies
with more examples. Furthermore, determining possible animal reservoir
hosts for effective control should be explored using molecular methods.
While it is obvious that the cost spent for the diagnosis and treatment
of leishmaniasis, an important public health problem, is higher than
the measures to prevent this disease, it is very sad that not enough
attention is paid to this issue in the world.
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