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2019| July-September | Volume 56 | Issue 3
Online since
July 9, 2020
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REVIEW ARTICLE
Malaria in Sri Lanka: Investigating causes of the recent elimination and making plans to prevent reintroduction
W.D. Hirunika N. Perera, P.A.D.H. Nayana Gunathilaka, Andrew W Taylor-Robinson
July-September 2019, 56(3):179-188
DOI
:10.4103/0972-9062.289390
PMID
:32655066
Sri Lanka is a country that has long suffered from epidemics of malaria. In this historical context, it is remarkable that in 2016 the Indian Ocean island nation was able to officially celebrate the elimination of this parasitic disease of major public health importance. The most devastating outbreak recorded in Sri Lanka was during 1934–35, when close to 80,000 human deaths were reported. Indoor residual spraying with the insecticides, DDT and malathion commenced in 1947 and was successful in causing a rapid decline in malaria incidence. However, poor vector control measures, resistance of mosquitoes to these insecticides and resistance of blood-stage
Plasmodium
parasites to the prevailing drugs used are considered the principal reasons for the occurrence of subsequent outbreaks. Despite this, Sri Lanka achieved the significant milestone of zero locally transmitted malaria cases in October 2012 and zero recorded deaths since 2007. Vector surveillance, parasitological examination, and clinical case management were collective effective activities that most likely led to elimination of malaria. Yet, there remains a high risk of reintroduction due to imported cases and an enduring vulnerability to vector transmission. In order to prevent re-establishment of malaria, continued financial support, sustained surveillance for vector species present in Sri Lanka and effective control of imported cases through rapid detection and early diagnosis are all required. In addition to these immediate practical priorities, further studies on vector biology and genetic variations that affect vectorial capacity would help to shed light on how to avoid reintroduction. This review affords an insight into the determinants of past malaria epidemics, strategies deployed to achieve and maintain the current status of elimination, lessons learnt from this success and plans to avoid resurgence of infection.
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3
RESEARCH ARTICLES
A novel quinoline-appended chalcone derivative as potential
Plasmodium falciparum
gametocytocide
Himank Kumar, Ishan Wadi, Vinod Devaraji, CR Pillai, Sujit Kumar Ghosh
July-September 2019, 56(3):189-199
DOI
:10.4103/0972-9062.289398
PMID
:32655067
Background & objectives:
Malaria has remained a global health problem despite the effective control and treatment measures. In the backdrop of drug resistance, developing novel hybrid molecules targeting the sexual stages (gametocytes) of the human malaria parasite
Plasmodium falciparum
is of great significance. Recently, chalcone- based polyphenols have generated a great interest in the malaria research community worldwide due to their ease of synthesis and significant biological activity. The primary objective of this study was to investigate the interaction of a newly synthesized quinoline-appended chalcone derivative (ADMQ) with gametocyte specific proteins, Pfg 27 and Pfs 25 and explore its
in vitro
gametocytocidal potential.
Methods:
The characterization of ligand-protein interactions at the atomistic level was done by a simulation strategy that combines molecular docking and molecular dynamics (MD) simulation in a coherent workflow. The X-ray crystal structure of Pfg 27 was retrieved from protein data bank and Pfs 25 was built using the Iterative Threading ASSembly Refinement (I-TASSER) server. The detailed interaction of both ADMQ and a known gametocytocidal agent, methylene blue (MB) (used as a positive control) with gametocyte proteins Pfg 27 and Pfs 25 was studied with a 50 ns explicit MD simulation. The ligand binding pose in terms of glide score, molecular mechanics-generalized born surface area (MM-GBSA) binding energies, protein-ligand root-mean-square-deviation (RMSD) and secondary structure elements (SSE) changes were analyzed accordingly. The direct effect of ADMQ on structural integrity of
P. falciparum
gametocytes was also examined using
in vitro
microscopy.
Results:
The analogous Glide score and MM-GBSA free energy of binding indicated stable interactions for both ADMQ and MB harboured in the active site of targeted gametocyte proteins, Pfg 27 and Pfs 25, separately. Explicit MD simulation by Desmond software package indicated similar distinguishable conformational changes in the active site of target polypeptide chain due to the specific accommodation of ADMQ molecule. The simulation also manifested comparable mechanistic profile in terms of protein-ligand RMSD and changes in secondary structure elements (SSE). Further, ADMQ treatment was found to adversely affect the structural integrity of gametocytes, which resulted in appearance of vesicles protruding from the gametocytes.
Interpretation & conclusion:
The consolidated
in silico
molecular modeling and
in vitro
study described herein may give an insight into the interaction patterns of quinoline-chalcone hybrids with critical gametocyte proteins in the mosquito. This study will possibly pave the way for further exploration of similar heterocyclic quinoline-chalcone hybrids to open up new avenues in drug candidate development against
P. falciparum
gametocytes.
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4
Use of cyclopoid copepods for control of
Anopheles
(Diptera: Culicidae) mosquito larvae to prevent re-emergence of malaria in Sri Lanka
Tharaka Ranathunge, W Abeyewickreme, M.C.M. Iqbal, Menaka Hapugoda
July-September 2019, 56(3):200-206
DOI
:10.4103/0972-9062.289393
PMID
:32655068
Background & objectives:
Although malaria is eliminated from Sri Lanka, there is a possible risk of spread from infected persons coming from malaria endemic countries. The presence of major and potential vectors in several parts of the country along with drug resistance, necessitates the identification of effective and novel control methods. The present study focused on identifying effective biological control agents for anopheline larvae using carnivorous copepods under laboratory and field conditions to prevent re-introduction of malaria in the country.
Methods:
Three copepod species, namely
Mesocyclops scrassus, Cyclops varicans
and
C. languides
collected from different areas in the country were cultured by adding supplementary food, and their predatory efficacy was evaluated under laboratory and field conditions.
Results:
Significant variation (
p
<0.05) was observed in predation rates of studied copepod species. The species
M. scrassus
showed the highest predacious efficiency, and consumed the highest number of anopheline larvae under laboratory and field conditions. Further,
M. scrassus
had higher survival rate than
C. varicans
and
C. languides
.
Interpretation & conclusion:
The results of the study suggest that the predatory copepod
M. scrassus
can be used as a bio-control agent for the control of
Anopheles
mosquitoes to prevent re-emergence of malaria in the country. Additional research is suggested to identify naturally available copepod species and their predatory efficacy.
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1
Molecular characterization of
Trypanosoma cruzi
and
Leishmania
spp. coinfection in mammals of Venezuelan coendemic areas
M Viettri, L Herrera, CM Aguilar, A Morocoima, J Reyes, M Lares, D Lozano-Arias, R García-Alzate, T Chacón, MD Feliciangeli, E Ferrer
July-September 2019, 56(3):252-262
DOI
:10.4103/0972-9062.289394
PMID
:32655075
Background & objectives: Trypanosoma cruzi
and
Leishmania
spp. are protozoans that cause American trypanosomiasis and leishmaniasis, respectively. In endemic foci where both diseases coincide, coinfection can occur. The objective of this work was the characterization of the parasites involved in coinfection in several endemic areas of Venezuela.
Methods:
Molecular characterization was done in 30 samples of several species of mammals
(Didelphis marsupialis, Equus mulus, Rattus rattus, Canis familiaris, Felis catus
, and
Sciurus granatensis)
from the states of Anzoategui, Cojedes and Capital District diagnosed with
T. cruzi
and
Leishmania
spp. coinfections. For the typing of
T. cruzi
DTUs, the markers of miniexon, 24Sa rDNA, 18Sa rDNA, and hsp60-PCR-RFLP (EcoRV) were used. Infection by
Leishmania
spp. was characterized by miniexon multiplex PCR for complexes of
Leishmania
and ITS1-PCR-RFLP (HaeIII,
Hha
I, and RsaI) for the identification of the species.
Results:
The
T. cruzi
TcI was present in 100% of the coinfected mammals, which included 76.7% of triple infection by
T. cruzi
TcI-complex–L.
(L) mexicana–L. infantum/chagasi
, 13.3% of double infection by
T. cruzi
TcI-L.
mexicana
and 10% of double infection by
T. cruzi
Tcl—
L. infantum/chagasi
.
Interpretation & conclusion:
These results suggest that the double or triple infection is a phenomenon existing in almost all the coendemics areas and mammals studied, which might influence the mechanisms of adaptation and pathogenicity of these parasites.
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3,155
365
10
Assessment of NS1 protein as an early diagnostic marker for Kyasanur forest disease virus
Pragya Yadav, Gouri Chaubal, Sarita Jena, Pratip Shil, Devendra Mourya
July-September 2019, 56(3):212-220
DOI
:10.4103/0972-9062.289392
Background & objectives:
Due to the emergence of Kyasanur forest disease (KFD) virus to new regions in India, there is an urgent need to develop an early diagnostic system, which is cost-effective and can be efficiently used with minimum paraphernalia. The non-structural-1 (NS1) protein is known to be an early diagnostic marker for flaviviruses. Furthermore, NS1 antigen capture ELISA kits developed using bacterially expressed dengue NS1 protein are commercially available.
Methods:
Based on the data available on dengue virus, West Nile virus and other flaviviruses, bacterially expressed Kyasanur forest disease virus (KFDV) NS1 protein and polyclonal serum raised against the NS1 protein in mice and rabbit were used to develop an antigen capture ELISA for early diagnosis of the virus. The feasibility of this ELISA was further tested using
in silico
predictions.
Results:
KFDV
NS1
gene was cloned, expressed and confirmed by SDS-PAGE and western blotting. An antigen detection ELISA was standardized and sensitivity and specificity was tested with other flaviviruses. KFDV acute phase 43 samples were tested and only two were found to be positive for KFDV NS1 antigen. Superimposition of KFDV NS1 and TBEV NS1 revealed a root mean square distance (RMSD) of ~0.79 Å covering 1220 backbone atoms. This implies that the structures are very similar in terms of 3D fold. The identity of amino acid composition between these proteins was 73.4% and similarity was 92.9%, as revealed from the pairwise comparison.
Interpretation & conclusion:
The study points out that the half-life, expression and secretion levels of KFDV NS1 protein are not sufficient enough for its use as early diagnostic marker. The protein may have to be expressed in eukaryotic host to counter the lack of glycosylation in bacterial plasmid based expression of proteins. Hence, bacterially expressed KFDV NS1 protein may not be an ideal early diagnostic marker for the virus.
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362
1
Circulation of Asian-I and Cosmopolitan genotypes of Dengue-2 virus in northeast India, 2016–2017
S Ujwal, S Sabeena, R Bhaskar, G D'Souza, D Santhosha, A Auti, R Kumar, S Ramachandran, Maity Hindol, A Aithal, Y Bhandari, A Jazeel, G Arunkumar
July-September 2019, 56(3):231-236
DOI
:10.4103/0972-9062.289402
PMID
:32655072
Background & objectives:
Dengue is a major public health problem in northeast India where the majority of the cases go unreported and undiagnosed. Even though all four dengue serotypes are reported, there is a dearth of information on genetic diversity. The present cross-sectional study was undertaken during 2016–17 to determine the genetic variance of dengue virus serotype 2 (DENV-2) based on the envelope (E) glycoprotein gene.
Methods:
The serum samples collected from the northeast parts of India, as a part of hospital-based acute febrile illness surveillance, were serotyped. Viral RNA was extracted from DENV-2 serum samples using QIAquick® RNA Extraction Kit. The E gene was amplified by conventional reverse-transcriptase polymerase chain reaction (RT-PCR) and the PCR products were sequenced.
Results:
The E glycoprotein gene of nine serum samples with high viral RNA concentration (Ct <25) was sequenced. The E gene sequences of eight DENV-2 strains from Assam and Meghalaya aligned with genotype IV (Cosmopolitan) and one strain from Tripura segregated with Asian-I genotype.
Interpretation & conclusion:
Ongoing laboratory-based surveillance is mandatory to understand the transmission dynamics of dengue in endemic countries. This study concluded that in northeast India, presently two distinct genotypes of DENV-2, namely genotype IVb (Cosmopolitan) and Asian-I genotype are in circulation.
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2,957
321
2
Effects of insecticide resistance on the reproductive potential of two sub-strains of the malaria vector
Anopheles coluzzii
Faty Amadou Sy, Ousmane Faye, Mawlouth Diallo, Ibrahima Dia
July-September 2019, 56(3):207-211
DOI
:10.4103/0972-9062.289401
PMID
:32655069
Background & objectives:
The emergence and spread of insecticide resistance in African malaria vectors raise concerns over the control of malaria disease. Therefore, the implementation of better control strategies need a thorough understanding of the effects and mechanisms of resistance on vector adaptation capacities. We studied the effects of insecticide resistance on the reproductive potential of two laboratory sub-strains of the malaria vector
Anopheles coluzzii
characterised by phenotypic resistance/susceptibility to DDT.
Methods:
The two sub-strains were selected from a laboratory strain of
An. coluzzii
using WHO test tubes. For each sub-strain, the number of produced and hatched eggs, developmental time, mosquito stages mortality, sex ratio and insemination rates after dissection of spermathecae were compared as measures of reproductive potential.
Results:
Overall, the susceptible sub-strain produced higher but not significant mean numbers of eggs. However, the mean numbers of hatched eggs, larvae, pupae and adults were significantly lower than those of the resistant substrain. The mean time from egg–hatching to adult–emergence, egg–flooding to hatching, I instar to pupae and pupae to adult were similar between the two sub-strains. The mortality rates at the pupal stage were significantly different between the two sub-strains. Of the dissected spermathecae, 85.1% of the females from the resistant sub-strain were fertilized compared to 66.1% of the females from the susceptible sub-strain (
p
<0.0001). The resistant sub-strain produced more females in comparison to the susceptible sub-strain (respective mean sex ratio 1.37 vs 1.03,
p
= 0.01).
Interpretation & conclusion:
The results show differential life history traits between the two sub-strains of the malaria vector
An. coluzzii
, particularly fertility, insemination rate and sex ratio. They may have varied implications for insecticide resistance spread, monitoring and management; and hence underscore the need of further investigations before any generalization.
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2
SHORT RESEARCH COMMUNICATION
A comparative study of the trends in epidemiological aspects of Lyme disease infections in Korea and Japan, 2011–2016
Won chang Lee, Myeong jin Lee, Kwang hoon Choi, Han sung Chung, Nong hoon Choe
July-September 2019, 56(3):268-271
DOI
:10.4103/0972-9062.289396
PMID
:32655077
Lyme disease (LD) is one of the most prevalent tick-borne emerging infections in North America, Europe, and far Eastern Asia including Korea and Japan. This study was undertaken with the aim of a comparative and quantitative analysis of the epidemiological aspects of LD infections in Korea and Japan from 2011 to 2016. The raw data analyzed in this study were obtained from the websites of the Korea Center for Disease Control and Prevention (KCDC), Korea, and the National Institute of Infectious Diseases (NIID), Japan. In total 65 cases of LD were observed with a cumulative incidence rate (CIR) of 0.22 per million population in Korea from 2011 to 2016. During the same period in Japan, there were 75 cases of LD with a CIR of 0.10 [significantly higher than that in Korea (
p
<0.01)]. Further, the results showed that in Korea, LD incidence was slightly higher in women than in men; but in Japan, the case was reverse, with incidence much higher in men than women. The proportion of cases differed significantly by age-specific adjusted groups within both countries (p <0.01). In both the countries, the incidence of LD was highest among those aged ≤20 yr (93.8% cases in Korea, and 94.7% cases in Japan). Cases peaked in autumn (46.7% of total cases) in Korea and in summer (60.0%) in Japan (
p
<0.01). The counties in rural areas had a significantly higher proportion of cases than the capital cities in both the countries (
p
<0.01). The study indicates that LD in Korea and Japan is an emerging zoonosis, and pose a serious risk to public health. The results underscore the continued emergency of LD and provide a basis for targeting prevention campaigns to a population with increasing incidence. Proper information, education and communication (IEC) activities can be helpful in reducing the spread of infection.
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RESEARCH ARTICLES
Synthesis of novel amodiaquine analogs and evaluation of their
in vitro
and
in vivo
antimalarial activities
Azar Tahghighi, Arezoo Rafie Parhizgar, Safoura Karimi, Mahboubeh Irani
July-September 2019, 56(3):221-230
DOI
:10.4103/0972-9062.289395
PMID
:32655071
Background & objectives:
Due to the rapid increase of drug resistance in
Plasmodium
parasites, there is a pressing need of developing new antiplasmodial drugs. In this study, new amodiaquine (AQ) analogs were synthesized, followed by an evaluation of their antiplasmodial activity.
Methods:
A new series of quinoline derivatives containing N-alkyl (piperazin-1-yl)methyl benzamidine moiety was synthesized by reacting 4-[(4-(7-chloroquinolin-4-yl)piperazin-1-yl)methyl]benzonitrile with appropriate primary amines. The synthesized compounds were investigated for inhibitory activity by inhibition test of heme detoxification (ITHD). Their antiplasmodial activity was then evaluated using the classical 4-day suppressive test (Peter’s test) against
Plasmodium berghei
-infected mice (ANKA strain).
Results:
The results showed that the percentage of heme detoxification inhibition in the active compounds was 90%. The most promising analogs, N-butyl-4-[(4-(7-chloroquinolin-4-yl)piperazin-1-yl)methyl]benzamidine (compound 1e), and 4-[(4-(7-chloroquinolin-4-yl)piperazin-1-yl)methyl)]-N-(4-methylpentan-2-yl)benzamidine (compound 1f) displayed 97.65 and 99.18% suppressions at the doses of 75 and 50 mg/kg/day, respectively. Further, the mean survival time of the mice treated with these compounds was higher than that of the negative control group.
Interpretation & conclusion: The
newly synthesized amodiaquine analogs presented sufficient antiplasmodial activity with excellent suppressions and high
in vitro
heme detoxification inhibition. Higher mean survival time of the mice treated with synthetic compounds further confirmed the
in vivo
antimalarial activity of these new AQ analogs. Therefore, these compounds have the potential to replace common drugs from 4-aminoquinoline class. However, further investigations such as pharmacokinetic evaluations, cytotoxicity, toxicity, and formulation seem to be necessary.
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Nifurtimox response of
Trypanosoma cruzi
isolates from an outbreak of Chagas disease in Caracas, Venezuela
Arturo Munoz-Calderon, Zoraida Díaz-Bello, José Luis Ramírez, Oscar Noya, Belkisyolé Alarcón de Noya
July-September 2019, 56(3):237-243
DOI
:10.4103/0972-9062.289397
PMID
:32655073
Background & objectives:
In Venezuela, Chagas disease (ChD) is considered a serious health problem, with about 6 million people at risk; and acute outbreaks due to oral transmission of Chagas Disease (OChD) are becoming increasingly important. In 2007 there was a major outbreak of OChD and although patients from this episode were treated with nifurtimox (Lampit®—Bayer), about 70% therapeutic failure was registered. These results led us to examine whether parasite’s drug susceptibility was related to this therapeutic failure.
Methods:
The
Trypanosoma cruzi
parasites were isolated by haemoculture of the peripheral blood drawn from the pre- and post-nifurtimox treated patients infected in the 2007 OChD outbreak at Caracas, Venezuela. The
in vitro
assays for drug testing were performed by the MTT methodology followed by calculation of inhibitory concentration-50 (IC
50
) values.
Results:
Parasite isolates obtained from the infected patients prior and after nifurtimox treatment when subjected to variable concentrations of the drug showed great heterogeneity in susceptibility with IC
50
values ranging from 4.07 ± 1.82 to 94.92 ± 7.24 μM.
Interpretation & conclusion:
The high heterogeneity in nifurtimox IC
50
values in the isolates and clones from the OChD patients, suggests that the therapeutic failure to nifurtimox could be due in part to a phenotypic variability that existed in the wild parasite population at the original source of contamination. Though, further pharmacological studies are needed to confirm the existence of natural nifurtimox resistance in the parasite.
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2,213
274
5
Human visceral leishmaniasis in northern Greece: Seroepidemiology and risk factors in endemic region
Dionysia Theocharidou, Efstratios Maltezos, Theodoros C Constantinidis, Anna Papa
July-September 2019, 56(3):244-251
DOI
:10.4103/0972-9062.289399
PMID
:32655074
Background & objectives:
Visceral leishmaniasis is endemic in Greece, with sporadic cases reported annually both in the mainland and in coastal areas. Seroepidemiological studies across Greece report seropositivity rates from 0.5 to 15%, in different parts of the country. The aim of the present study was to evaluate the
Leishmania
seropositivity rate of the general population of Drama prefecture, a rich in water supply region, in northern Greece.
Methods:
Serum samples collected from 347 healthy individuals were tested for IgG
Leishmania infantum
antibodies. Furthermore, 132 domestic dogs, clinically suspected to suffer from canine leishmaniasis, from all across the prefecture, were also evaluated.
Results:
Among 347 healthy individuals tested, 24 (6.9%) were positive for IgG
L. infantum
antibodies. Age, gender, occupational and leisure time activities didn’t show significant relation to IgG seropositivity, whereas low altitude of place of residency and residency at places with surface water were significantly related to IgG seropositivity. All seropositive individuals follow a geographic pattern, gathering themselves in Drama basin (rich in surface and underground water bodies), whereas canine leishmaniasis cases show a wide distribution across the prefecture.
Interpretation & conclusion:
Evaluation of both human seroprevalence and high incidence of canine leishmaniasis, as well as favorable landscape and climatic conditions of the study area, indicates that high level of clinical awareness need to be employed by physicians, as human and canine visceral leishmaniasis constitutes a serious public health concern.
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2,161
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1
Seroprevalence of West Nile virus in Khuzestan province, southwestern Iran, 2016–2017
Masoumeh Kalantari, Mostafa Salehi-Vaziri, Mohammad Hassan Pouriayevali, Vahid Baniasadi, Shokrollah Salmanzadeh, Morteza Kharat, Mehdi Fazlalipour
July-September 2019, 56(3):263-267
DOI
:10.4103/0972-9062.289391
PMID
:32655076
Background & objectives:
West Nile virus (WNV) is a neurotropic
Flavivirus
transmitted to humans through mosquito bites. As there is no specific antiviral treatment or approved vaccine against WNV, control and prevention of the infection is the best strategy to reduce the burden of WNV-related diseases. The circulation of WNV has been indicated in several regions of Iran including the Khuzestan province. Considering the complex ecology of WNV, the latest data are necessary for the implementation of preventive measures. Therefore, the present study was designed to provide updated information on the seroepidemiology of WNV in Khuzestan province.
Methods:
A total of 408 sera were taken from volunteers living in Khuzestan. The presence of specific immunoglobulin G (IgG) antibody against WNV was tested by the enzyme-linked immunosorbent assay (ELISA) method. All the data and participants’ demographic information were analyzed by SPSS and Esri’s ArcMap GIS software programs.
Results:
Anti-WNV IgG antibody was detected in 97 (23.8%) out of the 408 tested sera. The highest seropositivity rate was observed in cases aged between 20–29 yr and the lowest seropositivity rate was seen in those <19 yr of age (
p
= 0.001). There was no statistically significant association between WNV infection and gender, occupation, and educational level. The majority of positive cases were from the city of Ahvaz (47 cases, 48.4%) and Andimeshk (32 cases, 33%).
Interpretation & conclusion:
This study supports the earlier findings suggesting the circulation of WNV in Khuzestan province. Therefore, the implementation of an integrated surveillance system and training of health care workers and general population regarding the infection would be valuable to reduce the burden of possible outbreaks.
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2
CASE REPORTS
Crimean-Congo hemorrhagic fever virus Asia 2 genotype in Qeshm Island, southern Iran: A case report
Mehdi Fazlalipour, Vahid Baniasadi, Mohammad Hassan Pouriayevali, Tahmineh Jalali, Tahereh Mohammadi, Sanam Azad-Manjiri, Sara Azizizadeh, Motahareh Hosseini, Zahra Fereydouni, Mahsa Tavakoli, Mahsa Ghalejoogh, Sahar Khakifirouz, Mostafa Salehi-Vaziri
July-September 2019, 56(3):276-279
DOI
:10.4103/0972-9062.289389
PMID
:32655079
[ABSTRACT]
[FULL TEXT]
[PDF]
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[EPub]
[PubMed]
2,165
228
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Reversible splenial lesion in primary dengue fever
Ebenezer Daniel, Ajay Kumar Mishra, Pavithra Mannam, I Ramya
July-September 2019, 56(3):272-275
DOI
:10.4103/0972-9062.289400
PMID
:32655078
[ABSTRACT]
[FULL TEXT]
[PDF]
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[EPub]
[PubMed]
1,928
256
-
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