Loading

Clinical Research in Infectious Diseases

Dengue and Leptospira CoInfection

Research Article | Open Access Volume 5 | Issue 1 |

  • 1. Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, USA
  • 2. The Jackson Laboratory for Genomic Medicine, Farmington, CT
+ Show More - Show Less
Corresponding Authors
Jorge L. Cervantes, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX. 5001 El Paso Dr., El Paso, TX 79905, USA, Tel: 915-2154672
Abstract

Dengue and Leptospira not only share ecological niches, but also manifest with similar clinical presentation. Serologic evidence shows that co-infection by both pathogens is not uncommon in endemic areas. After performing a systematic search, we have here reviewed and analyzed a series of case reports on dengueLeptospira coinfection from around the world. 
We observed a positive correlation between bilirubin with hematocrit, and a negative correlation between platelets and hematocrit, and platelets and pulse, as well as between fever and creatinine, during co-infection. Mortality was a variable accounting for data clustering. Differences in age may also play a role in the mortality of co-infection with leptospirosis and dengue.
A physician’s consideration of the possibility of co-infection, and knowledge of the clinical presentation of when both infections are present, may allow for a rapid diagnosis and an adequate treatment plan that may reduce mortality.

Keywords

• Dengue

• Leptospirosis

• Co-infection

Citation

Ochoa MB, Hong BY, Cervantes JL (2020) Dengue and Leptospira Co-Infection.Clin Res Infect Dis 5(1): 1051.

INTRODUCTION

Dengue and Leptospirosis are two important causes of acute febrile illnesses in tropical and subtropical areas. An estimated 96 million cases of Dengue infections worldwide per year manifest clinically [1]. In the Americas, 2.35 million cases of Dengue were reported [2], of which 10,200 cases were diagnosed as severe and caused 1,181 deaths [2]. The incidence of Leptospirosis is close to a million cases per year worldwide, with almost 60,000 deaths [3]. The incidence of leptospirosis is highest in tropical and subtropical areas, particularly during outbreaks and in high-exposure risk groups [5].

Dengue can present with symptoms that may mimic other diseases such as leptospirosis which may complicate the diagnosis of a patient with acute febrile illness [5]. Dengue has a wide clinical spectrum and, in some cases, it may be difficult to differentiate it from other infections based solely on clinical-epidemiological criteria. Leptospirosis is an infectious febrile disease, that is also difficult to diagnose [6]. The similarity of their symptoms have shown that diagnostic confusion between these diseases may occur in routine clinical practice [7]. To the risk for misdiagnosis, we need to add the occurrence of co-infection, as these pathogens circulate in shared ecological niches [8].

In this study a collection of cases of co-infection with dengue virus and Leptospira spp. from around the world were analyzed in order to determine a clinical marker of severity or mortality.

 

MATERIALS AND METHODS

Literature search strategy

Literature search strategy comprised of a search on main data bases such as PubMed, EMBASE, and Google Scholar for case reports that included co-infection with dengue and leptospirosis, up to November 2018. Keywords used were lepto AND dengue, dengue fever AND lepto, dengue* AND lepto* , and DENV AND lepto* . No filters were used when using the databases. Case reports were picked based on the following guidelines, inclusion of a patient with diagnosed Dengue and Leptospira spp. co-infection and laboratory values reported for that patient. Case reports were excluded if they did not have a diagnosed case of Dengue and Leptospira spp. co-infection or if they did not provide patient information such as laboratory values or symptoms.

Data Retrieval and analysis

Case reports and research articles of co-infection with Dengue and Leptospira spp. were thoroughly analyzed by identifying all possible variables related to clinical presentation and laboratory results. Several variables were identified, including markers for clinical severity or mortality of co-infection with Dengue and Leptospira spp. Variables presented in the form of symptoms, physical exam findings, and laboratory results, including blood work and serology (Suppl Table 1).

Suppl. Table 1: Variables presented in the form of symptoms, physical exam findings, and laboratory results, including blood work and serology.

Country Year Author Days with Fever Bilirubin (mg/dL) ALT (U/L) AST (U/L) Creatinine (mg/dL) Hematocrit (%) Pulse (bpm) Platelets (cells/mm3)
India (30) 2002 Kaur 5 1.2 280 135        
Oman (31) 2008 Mohammad 3 2.1 116   7.04   70 122,000
Brazil (16) 2010 Meguins 5   521 1432       119,000
France (24) 2012 Cadelis   0.85 129 184 10.1   100 100,000
Puerto Rico (26) 2012 Sharp 6 4.77 140 285 2.86 26.1   70,000
India (22) 2013 Singh 5 8.2 342 230 6.2 39 120 38,000
Malaysia (32) 2013 Yong 6   55   1.14 39 100 67,000
India (33) 2014 Chopdekar 8         31.3   15,000
5             53,000
Puerto Rico (25) 2014 Perez-Rodriguez 3 6.9 68 389 1.55 23.3 135 34,000
2 5.19 351 1117 7.4 24.3 110 20,000
4 7.28 93 196 6.2 33   15,000
Sri Lanka (34) 2015 Dandeniya 5   103 39 1.65     77,000
Peru (35) 2015 Nunez 5   40 67 0.89 28 115 96,000
Sri Lanka (15) 2015 Wijesinghe 4 48.9 92 126 4.82 28.3 118 9,000
India (27) 2016 Pan 10 5.8            
10 2.6 104 127 1.3      
17 4 35   1.9      
ALT: Alanine Transaminase
AST: Aspartate Transaminase

Only variables that were in sufficient number (i.e. ≥5) were utilized for further analysis.

Statistical analysis

Whenever variables were in sufficient number (i.e. ≥5) they were included into a XY matrix to perform a correlation analysis, measuring a Pearson or Spearman correlation coefficient, if the data followed a Gaussian distribution or not. Tests for normality included D’Agostino, Shapiro-Wilk, and KS normality tests. The variables that were cross-analyzed were days with fever, bilirubin, ALT, AST, Creatinine, hematocrit, pulse, and platelets. In addition, a heat map showing correlation between the different variables was constructed using Morpheus (Broad Institute, MA).

To analyze mortality 2x2 tables were created to find a statistical significance between age, >25y/o and <25y/o, gender and death or survival. Data for each table was analyzed using a Fischer-exact test and a p-value was obtained. Calculations were done using GraphPad 7.0 software. A principal component analysis (PCA) was performed aiming to observe patterns in the data set containing the multiple variables listed in Table 1. A PCA plot was generated using R software [9].

RESULTS

Search strategy yielded a total of 13 studies included for analysis (Suppl. Figure 1).

Number of articles searched and retrieved

Suppl. Figure 1: Number of articles searched and retrieved

A table summarizing the demographic characteristics of these cases is presented in Table 1.

Table 1: A principal component analysis (PCA) was performed aiming to observe patterns in the data set containing the multiple variables

Country Year Author Sex Age Death
India (30) 2002 Kaur Female 15 No
Oman (31) 2008 Mohammad Male 41 No
Brazil (16) 2010 Meguins Male 41 No
France (24) 2012 Cadelis Female 46 Yes
Puerto Rico (26) 2012 Sharp Male 42 Yes
India (22) 2013 Singh Male 40 Yes
Malaysia (32) 2013 Yong Male 47 No
India (33) 2014 Chopdekar Male 4 No
Female 7 No
Puerto Rico (25) 2014 Perez-Rodriguez Male 22 Yes
Male 64 Yes
Male 67 Yes
Sri Lanka (34) 2015 Dandeniya Male 49 No
Peru (35) 2015 Nunez Female 10 No
Sri Lanka (15) 2015 Wijesinghe Male 52 Yes
India (27) 2016 Pan Male 22 Yes
Male 64 Yes
Male 67 Yes

Supplementary Table 1 shows the variables analyzed across the reported cases. Several variables were observed to correlate with each other. A heat map showing correlation between the different variables is displayed in Figure 1A.

Correlation between main variables in Dengue + Leptospira co-infection cases. A Heatmap showing correlation between the different analyzed variables. B-D Variables that presented a high correlation coefficient and statistical significance.

Figure 1: Correlation between main variables in Dengue + Leptospira co-infection cases. A Heatmap showing correlation between the different analyzed variables. B-D Variables that presented a high correlation coefficient and statistical significance.

Those that presented with a high correlation coefficient and statistical significance are presented in Figure 1 B-D. When using fever as the X value, correlation analysis compared the correlation between AST vs. bilirubin, and pulse vs. platelets. The analysis between hematocrit vs. platelets showed a strong negative correlation (Spearman coefficient -0.810, p = 0.02) (Figure 1B). This negative correlation showed that as platelets numbers decreased, hematocrit increased. When analyzing platelets vs. pulse, the analysis displayed a strong negative correlation (Spearman -0.746, p = 0.027) (Figure 1C). The negative correlation displays that as pulse increases, the number of platelets decreases. Analysis on hematocrit vs. bilirubin displayed a strong positive correlation (Pearson 0.831, p=0.020), indicating that as bilirubin increases, hematocrit also increases (Figure 1D). Using bilirubin as the X value, a correlation analysis of pulse vs platelets displayed a strong negative correlation of (Pearson -0.735, p = 0.030). Using ALT or AST as the X value, a strong positive correlation was observed when analyzing platelets vs. pulse (Spearman -0.810, p= 0.011). When using ALT as the X value, a Spearman correlation was done to analyze fever and creatinine. The data showed a moderate negative correlation (-0.521, p = 0.035).

Two contingency tables were built to analyze joint distribution between age, gender and death.

Table 2: Displays the analysis between age (20y/o) and the outcome of death or survival.

  Death Survival
<20y/o 0 5
>20y/o 7 6
Fischer’s exact test (p = 0.04)

Table 2 displays the analysis between age (20y/o) and the outcome of death or survival. Given the small numbers, a Fisher’s exact test was performed, with statistical significance in death/survival between these two age groups (p = 0.04). When performing the analysis between gender vs. outcome (death or survival) (Table 3),

Table 3: When performing the analysis between gender vs. outcome (death or survival) no statistical significant difference was found

  Death Survival
Male 6 7
Female 1 4
Fischer’s exact test (p = 0.5)

no statistical significant difference was found.

A PCA on the data set containing the multiple variables listed in Table 1, revealed clustering of data with mortality as a variable accounting for clustering towards positive direction of PC2 (eigen values for PC1 and PC2, 1.51 and 1.09 respectively). A PCA plot showing clustering by mortality is shown in Figure 2.

Principal component analysis (PCA) plot showing clustering for mortality amongst analyzed cases. Filled circles (?) represent dead cases, while open circles (•) represent those who survived.

Figure 2: Principal component analysis (PCA) plot showing clustering for mortality amongst analyzed cases. Filled circles (°) represent dead cases, while open circles (·) represent those who survived.

DISCUSSION

As both Dengue and Leptospira spp. share ecological niches in the tropics, clinicians need to be aware of the possibility of coinfection, especially in areas of endemicity [5,10,11]. Co-infection of dengue with leptospirosis can sometimes be overlooked due to their similar clinical presentations [5].

Immunological markers could help differentiate the two infections [12], but these are not routinely performed and would certainly be costly. Markers for severity or mortality dependent on antigen-based serologic testing or nucleic detection for both Dengue and Leptospira spp. are also costly and time consuming [13]. A timely clinical suspicion for either infection, or for coinfection, is of the essence. A rapid confirmation of leptospirosis would lead into prompt antibiotic treatment, while confirmation of dengue fever would lead to close platelet count monitoring and initiation of supportive measures.

A prospective study in 100 cases of dengue and 100 cases of leptospirosis, found oliguria, icterus, muscle tenderness, anemia, leukocytopenia, thrombocytopenia, elevated erythrocyte sedimentation rate (ESR), acute renal failure (ARF) and hypoalbuminemia to be more commonly in leptospirosis in comparison to dengue (14). ARF, hyperbilirubinaemia, acute respiratory distress syndrome (ARDS), creatine kinase (CK) elevation and thrombocytopenia were predictors of death in leptospirosis, while thrombocytopenia, ARDS and ARF predictors of death in dengue. Their predictive model to distinguish between the two infections found leucocytosis, and increased ESR, creatinine, bilirubin, CK, and decreased albumin to be more indicative of leptospirosis at presentation compared to dengue [14]. A recent study aiming to identify predictors of dengueleptospirosis infection, did not find any difference between hematocrit, platelet count, ALT, AST, but observed an increase in creatinine phosphokinase (CPK) in leptospirosis-dengue cases retrospectively [10]. Unfortunately, only two of the case reports review in this study had a value for CPK, one showing enzyme elevation [15], and the other, a normal value [16].

A decline in liver function is a common feature of leptospirosis [17] and dengue fever [18]. Hepatic damage can be due to decrease in perfusion occurring in patients with dengue or leptospirosis [19]. The decrease in blood volume will also lead to an increased hematocrit level [19], which is evident with the strong positive correlation we found between hematocrit and bilirubin or thrombocytopenia. Hepatic inflammation may translate clinically in symptoms like nausea, vomiting, or diarrhea, observed in leptospirosis with dengue fever or its more severe presentation, dengue hemorrhagic fever (DHF) [11].

Vascular damage [17], which encompasses endothelial damage and surrounding inflammation, is also a common feature of leptospirosis and dengue [20]. This leads to plasma leakage, a phenomenon in leptospirosis and DHF [11,12]. DHF features plasma leakage and severe bleeding [18]. The decrease in platelet count leads to increased bleeding which in turn increases the risk of the patient developing shock. As our data indicated, thrombocytopenia is associated with an increase in pulse, indicative of the hemodynamic instability occurring in DHF [21] (Suppl. Figure 2). Our findings point out that Leptospiradengue co-infected cases are more severe cases, possible due to a synergistic effect of the inflammatory mediators induced in the host the presence of both pathogens [20,21].

Intracranial hemorrhage was the main presentation of one of the cases of coinfection with leptospirosis and dengue [22]. Bleeding in the lung, occurs at the alveolar level in leptospirosis [17,23]. Although alveolar hemorrhage is well described in some of the coinfection reports analyzed [15,24], it can only be inferred from the radiologic description of some others [25-27], thus limiting our analysis.

Mortality, as a variable, clustered the data, as observed from the PCA output. Our mortality analysis also showed that an outcome of death due to leptospirosis-dengue coinfection was higher in younger individuals. It could be that a stronger immune response occurring in younger patients leads to a cytokine storm [28] that translates into a more severe disease (29) with a poorer prognosis.

Despite the fact that dengue and Leptospira infection can both present with similar symptoms and laboratory findings which can contribute to a difficult diagnosis, our findings are suggestive that some of these biomarkers co-regulate between each other, accentuating their damage, especially in younger patients. Education and awareness of these variables by physicians in endemic areas for both diseases is imperative for close and rapid monitoring and treatment.

CONCLUSIONS

After analyzing the series of cases of dengue and leptospirosis reported around the world, we observed a positive correlation between bilirubin with hematocrit, and a negative correlation between platelets and hematocrit, and platelets and pulse, as well as between fever and creatinine, during co-infection. Mortality was a variable accounting for data clustering. Differences in age may also play a role in the mortality of co-infection with leptospirosis and dengue.

A physician’s consideration of the possibility of co-infection, and knowledge of the clinical presentation of when both infections are present, may allow for a rapid diagnosis and an adequate treatment plan that may reduce mortality.

REFERENCES

1. Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, et al. The global distribution and burden of dengue. Nature. 2013; 496: 504-57.

2. Guo C, Zhou Z, Wen Z, Liu Y, Zeng C, Xiao D, et al. Global Epidemiology of Dengue Outbreaks in 1990-2015: A Systematic Review and Meta-Analysis. Front Cell Infect Microbiol. 2017; 7: 317.

3. Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, et al. Global Morbidity and Mortality of Leptospirosis: A Systematic Review. PLoS neglected tropical diseases. 2015; 9: e0003898.

4. Lau CL, Townell N, Stephenson E, van den Berg D, Craig SB. Leptospirosis. Australian journal of general practice. 2018; 47: 105- 110.

5. Mishra B, Singhal L, Sethi S, Ratho RK. Leptospirosis coexistent with dengue Fever: a diagnostic dilemma. Journal of global infectious diseases. 2013; 5: 121-122.

6. Bandara M, Ananda M, Wickramage K, Berger E, Agampodi S. Globalization of leptospirosis through travel and migration. Globalization and health. 2014; 10: 61.

7. Oliveira AC FR, Praciano CC, Araújo FM, Cavalcanti LP, Colares JK. Recognition of leptospirosis in dengue suspected cases during outbreak in Ceará State, Brazil. African Journal Microbiological Research. 2014; 8: 1789-1792.

8. Garcia-Ruiz D, Martinez-Guzman MA, Cardenas-Vargas A, Marino-Marmolejo E, Gutierrez-Ortega A, Gonzalez-Diaz E, et al. Detection of dengue, west Nile virus, rickettsiosis and leptospirosis by a new real-time PCR strategy. SpringerPlus. 2016; 5: 671.

9. Foundation R. 2018.

10. Suppiah J, Chan SY, Ng MW, Khaw YS, Ching SM, Mat-Nor LA, et al. Clinical predictors of dengue fever co-infected with leptospirosis among patients admitted for dengue fever - a pilot study. J Biomed Sci. 2017; 24: 40. 

11. Dircio Montes Sergio A, Gonzalez Figueroa E, Maria Saadia VG, Elizabeth SH, Beatriz RS, Altuzar Aguilar Victor M, et al. Leptospirosis prevalence in patients with initial diagnosis of dengue. Journal of tropical medicine. 2012; 2012: 519701.

12. Conroy AL, Gelvez M, Hawkes M, Rajwans N, Liles WC, Villar-Centeno LA, et al. Host biomarkers distinguish dengue from leptospirosis in Colombia: a case-control study. BMC infect Dis. 2014; 14: 35.

13. Canal E, Pollett S, Heitzinger K, Gregory M, Kasper M, Halsey E, et al. Detection of human leptospirosis as a cause of acute fever by capture ELISA using a Leptospira interrogans serovar Copenhageni (M20) derived antigen. BMC infectious diseases. 2013; 13: 438.

14. Varma MD, Vengalil S, Vallabhajosyula S, Krishnakumar PC, Vidyasagar S. Leptospirosis and dengue fever: a predictive model for early differentiation based on clinical and biochemical parameters. Tropical doctor. 2014; 44: 100-102.

15. Wijesinghe A, Gnanapragash N, Ranasinghe G, Ragunathan MK. Fatal co-infection with leptospirosis and dengue in a Sri Lankan male. BMC research notes. 2015; 8: 348.

16. Meguins LC, HO dMJ. Leptospirosis and dengue co-infection in a Brazilian Amazon patient. Rev Pan-Amaz Saude. 2010; 1: 97-99.

17. Murray GL. The molecular basis of leptospiral pathogenesis. Current topics in microbiology and immunology. 2015; 387: 139-185.

18. Wan SW, Lin CF, Yeh TM, Liu CC, Liu HS, Wang S, et al. Autoimmunity in dengue pathogenesis. J Formos Med Assoc.2013; 112: 3-11.

19. Fernando S, Wijewickrama A, Gomes L, Punchihewa CT, Madusanka SD, Dissanayake H, et al. Patterns and causes of liver involvement in acute dengue infection. BMC infect Dis. 2016; 16: 319.

20. Priya SP, Sakinah S, Sharmilah K, Hamat RA, Sekawi Z, Higuchi A, et al. Leptospirosis: Molecular trial path and immunopathogenesis correlated with dengue, malaria and mimetic hemorrhagic infections. Acta tropica. 2017; 176: 206-223.

21. de Azeredo EL, Monteiro RQ, de-Oliveira Pinto LM. Thrombocytopenia in Dengue: Interrelationship between Virus and the Imbalance between Coagulation and Fibrinolysis and Inflammatory Mediators. Mediators Inflamm. 2015; 2015: 313842.

22. Singh RK, Ghatak T, Baronia AK, Garg P. Intracranial hemorrhage in a patient coinfected with dengue and leptospirosis. J Neurosci Rural Pract. 2013; 4: 366-367.

23. Im JG, Yeon KM, Han MC, Kim CW, Webb WR, Lee JS, et al. Leptospirosis of the lung: radiographic findings in 58 patients. AJR Am J Roentgenol. 1989; 152: 955-959.

24. Cadelis G. Intra-alveolar hemorrhage associated with dengue and leptospirosis. Rev Pneumol Clin. 2012; 68: 323-326.

25. Perez-Rodriguez NM, Galloway R, Blau DM, Traxler R, Bhatnagar J, Zaki SR, et al. Case series of fatal Leptospira spp./dengue virus co-infections-Puerto Rico, 2010-2012. Am J Trop Med Hyg. 2014; 91: 760-765.

26. Sharp TM, Bracero J, Rivera A, Shieh WJ, Bhatnagar J, Rivera-Diez I, et al. Fatal human co-infection with Leptospira spp. and dengue virus, Puerto Rico, 2010. Emerging infectious diseases. 2012; 18: 878-880.

27. Pan K, Roy U, Kumar S a, A P. Leptospirosis and dengue coinfection: Report of three cases with review of literature. Annals of Tropical Medicine and Public Health. 2016; 9: 119-121.

28. Cagliero J, Villanueva S, Matsui M. Leptospirosis Pathophysiology: Into the Storm of Cytokines. Front Cell Infect Microbiol. 2018; 8: 204.

29. Uno N, Ross TM. Dengue virus and the host innate immune response. Emerg Microbes Infect. 2018; 7: 167.

30. Kaur H, John M. Mixed infection due to leptospira and dengue. Indian journal of gastroenterology: official journal of the Indian Society of Gastroenterology. 2002; 2: 206.

31. Mohammad E, Mohsin N, Al-Abri S, Al-Abaidani I, Jha A, Camble P, et al. Acute Renal Failure in a Patient with both Leptospirosis and Dengue Fever. Oman Med J. 2008; 23: 101-103.

32. Yong LS, Koh KC. A case of mixed infections in a patient presenting with acute febrile illness in the tropics. Case reports in infectious diseases. 2013; 2013: 562175.

33. Chopdekar K, Patil S, Lilani S, Joshi A, Chowdhary A. Concomitant leptospirosis and dengue infections. Journal of the Indian Academy of Clinical Medicine. 2014; 15: 258-259.

34. Dandeniya C, Ralapanawa U, Jayalath T, Kularatne S. Atypical manifestations of dengue infection due to co-infection with either hepatitis A or leptospirosis: two case reports. Sri Lankan Journal of infectious Diseases. 2015; 5: 36-40.

35. Nunez-Garbin A, Espinoza-Figueroa J, Sihuincha-Maldonado M, Suarez-Ognio L. [Coinfection of dengue and leptospirosis in a girl from the peruvian amazon]. Revista peruana de medicina experimental y salud publica. 2015; 32: 179-182.

Ochoa MB, Hong BY, Cervantes JL (2020) Dengue and Leptospira Co-Infection.Clin Res Infect Dis 5(1): 1051.

Received : 12 Feb 2020
Accepted : 21 Feb 2020
Published : 24 Feb 2020
Journals
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X