Recent Patents on Anti-Infective Drug Discovery (v.10, #1)

Meet Our Editorial Board Member by Michael R. Hamblin (1-1).

Preface by Dieter Kabelitz (2-2).

Human Anthrax as a Re-Emerging Disease by Mehmet Doganay, Hayati Demiraslan (10-29).
Anthrax is primarily a disease of herbivores and the etiological agent is B. anthracis which is a gram-positive, aerobic, spore-forming, and rod shaped bacterium. Bacillus anthracis spores are highly resistant to heat, pressure, ultraviolet and ionizing radiation, chemical agents and disinfectants. For these reasons, B. anthracis spores are an attractive choice as biological agents for the use of bioweapon and/or bioterrorism. Soil is the main reservoir for the infectious agent. The disease most commonly affects wild and domestic mammals. Human are secondarily infected by contact with infected animals and contaminated animal products or directly expose to B. anthracis spores. Anthrax occurs worldwide. This infection is still endemic or hyperendemic in both animals and humans in some part of areas of the world; particularly in Middle East, West Africa, Central Asia, some part of India, South America. However, some countries are claiming free of anthrax, and anthrax has become a re-emerging disease in western countries with the intentional outbreak. Currently, anthrax is classified according to its setting as (1) naturally occurring anthrax, (2) bioterrorism-related anthrax. Vast majority of human anthrax are occurring as naturally occurring anthrax in the world. It is also a threaten disease for western countries. The aim of this paper is to review the relevant patents, short historical perspective, microbiological and epidemiological features, clinical presentations and treatment.

Rabies in South Asia: Fighting for Elimination by Fazle-Rabbi Chowdhury, Ariful Basher, Mohammad R. Amin, Nazia Hassan, Mohammad i. Patwary (30-34).
South Asia is regarded as the hot spot for the tourist and travelers. Unfortunately, three big countries (India, Pakistan and Bangladesh) of this region belong to top five rabies endemic countries of the world. Around 55,000 people die of rabies every year globally and 45% of them belong to South and South East Asia. Countries are now working on the elimination of rabies by the year 2020. Elimination of animal rabies is the pivotal of controlling human rabies. Dog (primary source) registration, population control and mass vaccination are the different ways of eliminating animal rabies. Pre (for risk groups including travelers) and post-exposure vaccine is the core for controlling human rabies. Post-exposure vaccine consists of nerve tissue vaccine and tissue culture vaccine. Due to low antigenicity and post-vaccine neurological complications all countries of South Asia except Pakistan have phased out the production and use of nerve tissue vaccine. To reduce the cost intramuscular regimen is now largely replaced by intradermal regimen and equine rabies immunoglobulin will probably replace human immunoglobulin in future for category III animal bite. 'SAARC' took initiatives for rabies elimination through 'SAARC development fund' which would hopefully play a vital role in regional collaboration to make the region rabies free.

Ocular Toxocariasis: New Diagnostic and Therapeutic Perspectives by Dayron F. Martínez-Pulgarin, Marcela Munoz-Urbano, Luz D. Gomez-Suta, Olinda M. Delgado, Alfonso J. Rodriguez-Morales (35-41).
Purpose: To provide an updated insight of concepts regarding the overview, epidemiology, risk factors, clinical manifestations, diagnosis, treatment and prevention of ocular toxocariasis. Design: Perspective of literature review. Methods: Review and synthesis of literature about toxocariasis, with interpretation and perspective. A literature search for 'ocular toxocariasis' was performed using PubMed, ScienceDirect, Scopus, SciELO and LILACS databases. Results: Mild to moderate infections are frequently reported in ocular toxocariasis which usually occurs in children and typically presents as unilateral vision impairment, blindness is common and could present invasion of the retina. There are three groups of presentation of toxocariasis (according to the physical examination): chronic endophthalmitis, posterior granuloma and peripheral granuloma. Standard diagnosis of ocular toxocariasis is based on the identification of clinical signs, supported by additional diagnostic methods. Regarding treatment, there is no commonly accepted regimen but most of the authors prefer to use steroids and anthelminthic agents, but nowadays there are no standardized parameters in terms of dosage, duration and route of administration. Surgery has been recommended in some cases. Conclusion: Toxocariasis is still a problem of public health, particularly in developing countries with an increasing epidemiological burden in terms of morbidity and mortality and most of the authors agree on the utmost relevance of its prevention. Clinical experience and suspicion of ophthalmologists make an important role in its diagnosis, but always with supportive diagnostic methods. Additional studies should explore new therapeutic options for toxocariasis.

Geographical and Occupational Aspects of Leptospirosis in the Coffee-Triangle Region of Colombia, 2007-2011 by Laura M. Garcia-Ramirez, Jasmin Y. Giraldo-Pulgarin, Nelly Agudelo-Marin, Yeimer A. Holguin-Rivera, Sebastian Gomez-Sierra, Paola V. Ortiz-Revelo, Nestor J. Velasquez-Bonilla, Yohama Caraballo-Arias, Alvaro Mondragon-Cardona, Carlos O. Lozada-Riascos, Alfonso J. Rodríguez-Morales (42-50).
Background: There are few studies occupationally profiling as well as using Geographic information system (GIS) to map human leptospirosis. There are no detailed, municipality-level, epidemiological maps in Colombia neither in South America. We developed such maps for the Coffee-triangle region, Colombia and assess some occupational issues. Methods: surveillance cases data (2007-2011) were used to estimate the annual incidence rates (cases/100,000 population) of leptospirosis to develop the first maps of disease in the 53 municipalities of the Coffee-triangle region of Colombia. GIS used was Kosmo® 3.1. Five thematic maps were developed according to municipalities and years. Using labor official information, analyses between agriculture (harvested areas) with disease occurrence was done (linear regression). Results: Between 2007 and 2011, 786 cases were reported (77.8% from one department, Risaralda), for a cumulated rate of 32.18 cases/100,000 population. The highest rate was reported in the less developed municipality of one department (Pueblo Rico, Risaralda) with 1535.05 cases/100,000 population (187 cases, 2009). Armenia (Quindio department capital city), reported 23.41 cases/100,000pop (2011). In those patients with identified occupations, 33.3% were agriculture workers, finding a significant relationship between the number of cases in 2008 and the harvested area by municipality (r2=0.48; p=0.0083). Conclusion: one of the 53 municipalities contributed with almost a quarter of the cases. Agriculture was significantly associated with the incidence. Use of GIS-based epidemiological maps allow to focus actions in prevention and control for risk zones for leptospirosis which still represents a significant issue in the region and Colombia, particularly in agriculture workers.

Dengue Patients Treated with Doxycycline Showed Lower Mortality Associated to a Reduction in IL-6 and TNF Levels by Terry M. Fredeking, Jorge E. Zavala-Castro, Pedro Gonzalez-Martinez, William Moguel-Rodríguez, Ernesto C. Sanchez, Michael J. Foster, Fredi A. Diaz-Quijano (51-58).
Objective: To determine the effect of doxycycline treatment on cytokine levels, including tumor necrosis factor (TNF) and interleukin 6 (IL-6), and mortality in dengue patients at high risk of complication.
Methods: A group of dengue hemorrhagic fever patients (n=231) were randomized to receive either standard supportive care or supportive care in addition to oral doxycycline twice daily for 7 days. Dengue virus infection was confirmed by PCR using multiple primers. Serum samples were obtained at days 0, 3, 5 and 7 and tested for levels of TNF and IL-6.
Results: Doxycycline-treated group presented a 46% lower mortality than that observed in the untreated group (11.2% [13/116] vs 20.9% [24/115], respectively, p=0.05). Moreover, administration of doxycycline resulted in a significant (p<0.01) decrease in levels of TNF and IL-6 versus controls in the tests performed during follow-up (day 3, 5 and 7). Patients who died in both groups possessed significantly (p<0.01) higher levels of TNF and IL-6 compared to those who survived at all-time points.
Conclusion: The above findings suggest that doxycycline can provide a clinical benefit to dengue patients at high risk of complications. This effect could be mediated by decreasing pro-inflammatory cytokine levels.

Leptospirosis in an Urban Setting: Cases Diagnosed at a Private Medical Center of Western Colombia, 2008-2012 by Mar&#237;a M. Ramirez-Ramirez, Olga M. Leon-Castaneda, Alfonso J. Rodriguez-Morales (59-63).
Introduction: Leptospirosis has reemerged as significant threat particularly in developing countries, including those in Latin America. Data from Colombia is still limited and there are no published studies in the Western area of the country. Methods: Data on suspected cases were collected over the study period (2008- 2012). Cases were diagnosed clinically and confirmed by ELISA IgG and microscopic agglutination test (MAT) (titers ≥1:400). Results: During the study period 264 suspected cases of leptospirosis were found. From those, 8.33% (22 cases) were microbiologically confirmed. Number of suspected cases increased in the period from 20 (2008) (40 cases/100,000 consultations) to 58 (2012) (120 cases/100,000 consultations). Regard sex distribution, 62.5% were males, 14% in the age group 21-30 y-old, from confirmed cases 95% live in urban areas of Pereira, 25.7% own dogs and 13.2% cats, 32.3% reporting rats at home as well 22.7% at work places. From confirmed cases 72.7% were hospitalized. Clinical findings found were: fever (60.2%), myalgias (47%), and headache (41.9%), among others. All the cases corresponded to Leptospira interrogans. Regard the serovars, in these patients 6 were identified: Australis (54.5%), Icterohaemorrhagiae (45.5%), Canicola (45.5%), Panama (45.5%), Pomona (36.3) and Grippotyphosa (1%). Thirty nine percent of the patients received antimicrobial therapy, 50% ceftriaxone. No deaths occurred. Conclusion: Leptospirosis is an emerging infectious disease that has changed from an occupational disease of veterinarians, farmers, butchers, and other animal handlers to a cause of epidemics in poor and decayed urban communities in developing countries, including those in Latin America such as Colombia.

Letter to Editor: From Imported to an Endemic Disease: Impact of Chikungunya Virus Disease in the Hospital Epidemiology, Tolima, Colombia, 2014-2015 by Carlos E. Jimenez-Canizales, David A. Medina-Gaitan, &#195;lvaro E. Mondragon-Cardona, Alfonso J. Rodriguez-Morales (64-66).