Volume 32, Issue 3, 2024
Editorial
The Resurgence of Mpox: A New Global Health Crisis
Acosta-España Jaime David,
Bonilla-Aldana D. Katterine,
Luna Camila,
Rodriguez-Morales Alfonso J.
Not available
Review
Multisystem Inflammatory Syndrome of the Adults (MIS-A) - The undercover threat for young adults. A systematic review and meta-analysis of medical cases.
Michailides Christos,
Papantoniou Konstantinos,
Paraskevas Themistoklis,
Lagadinou Maria,
Marangos Markos,
Kavvousanos Michael,
Michailidou Pinelopi,
Velissaris Dimitrios
Background: COVID-19 related syndromes are not yet well described and understood. Multisystem inflammatory syndrome of the adults (MIS-A) is a recently characterized syndrome affecting multiple organs of young adults, causing serious complications, even shock and death.
Objectives: To determine the clinical characteristics, course, and complications of MIS-A in a systematic way and summarize currently used treatments.
Methods: Literature search in March 2023 in PubMed and Scopus databases. Case reports and case-series that fulfilled the CDC criteria for MIS-A were eligible for inclusion.
Results: A total of 71 patients from 60 reports were included. 66% of the patients were male and the mean age of the synthetic cohort was 32.9 years old. The majority (70.4%) of the enrolled cases had no significant medical history. MIS-A was diagnosed after a median of 4 weeks period. All but two patients presented with cardiac symptoms, while the most common secondary diagnostic criterion was abdominal pain, vomiting or diarrhea followed by shock or hypotension. Heart failure therapy and immunomodulation were used as therapeutic options. Although more than half of the cohort was admitted to the Intensive Care Unit (ICU) (n=39) only 4 deaths were reported.
Conclusion: MIS-A can affect patients independently of age, sex, and co-morbidity status, resulting in serious complications, often including severe cardiac disease, shock, acute kidney injury and sometimes death. It can occur immediately after SARS-COV-2 acute infection until two months later, usually manifesting four weeks after acute disease.
Clostridioides difficile infection: an update
Salvati Federica,
Catania Francesca,
Murri Rita,
Fantoni Massimo,
Torti Carlo
Clostridioides difficile (C. difficile) is a Gram-positive, spore-forming anaerobic bacterium emerged as a leading cause of diarrhea globally. CDI’s (Clostridioides difficile infection) impact on healthcare systems is concerning due to high treatment cost and increased hospitalisation time. The incidence of CDI has been influenced by hypervirulent strains such as the 027 ribotype, responsible for significant outbreaks in North America and Europe. CDI's epidemiology has evolved, showing increased community-acquired cases alongside traditional hospital-acquired infections. Mortality rates remain high, with recurrent infections further elevating the risk. Transmission of C. difficile primarily occurs via spores, which survive in healthcare settings and play a pivotal role in transmission. Not only health workers, but also the food chain could have a significant impact on the transmission of infection, although no confirmed foodborne cases have been documented. Pathogenicity of C. difficile involves spore germination and toxin production. Toxins A and B can cause cellular damage and inflammatory responses in the host, leading to colitis. Clinical picture can range from mild diarrhea to fulminant colitis with toxic megacolon, and bowel perforation.
Risk factors for CDI include antibiotic exposure, advanced age, hospitalization, and use of proton pump inhibitors. Patients who experience abdominal surgery or patients with inflammatory bowel disease (IBD) are particularly susceptible due to their compromised gut microbiota. Management of CDI has evolved, with fidaxomicin emerging as a superior treatment option over vancomycin for initial and recurrent infections due to its reduction of recurrence rate. Faecal microbiota transplantation (FMT) is effective for recurrent CDI, restoring gut eubiosis. Bezlotoxumab, a monoclonal antibody against C. difficile toxin B, has shown promise in reducing recurrence rates. Severe cases of CDI may require surgical intervention, particularly in instances of toxic megacolon or bowel perforation. In conclusion, CDI remains a significant clinical entity. Further research are needed to improve patients’ outcome and reduce the burden on healthcare systems.
Prevalence of latent tuberculosis infection (LTBI) in healthcare workers in Latin America and the Caribbean: systematic review and meta-analysis.
Meregildo-Rodriguez Edinson Dante,
Ortiz-Pizarro Mariano,
Asmat-Rubio Martha Genara,
Rojas-Benites Mayra Janett,
Vásquez-Tirado Gustavo Adolfo
Background: Tuberculosis remains a significant global health concern, and healthcare workers (HCWs) face a high risk of acquiring latent tuberculosis infection (LTBI) through occupational exposure. In the Latin American and Caribbean (LAC) region, where the burden of tuberculosis is substantial, understanding the prevalence of LTBI among HCWs is crucial for effective infection control measures. Therefore, we conducted a systematic review and meta-analysis to estimate the prevalence of LTBI among HCWs in LAC countries.
Methods: Our search included MEDLINE, Scopus, EMBASE, Web of Science, and Google Scholar databases, focusing on relevant English-language records. We looked for observational studies from inception until December 2023.
Results: Our analysis included 38 studies representing 15,236 HCWs and 6,728 LTBI cases. These studies spanned the period from 1994 to 2023 and were conducted in Brazil, Peru, Cuba, Colombia, Trinidad and Tobago, Mexico, and Chile. The mean prevalence of LTBI among HCWs was 35.32% (range 17.86-56.00%) for interferon-gamma release assay (IGRA) and 43.67% (range 6.68-70.29%) for tuberculin skin test (TST). The pooled prevalence of LTBI among HCWs was 34.5% (95% CI 25.4-44.1%) for IGRA and 43.0% (95% CI 35.5-50.7%) for TST. When considering both IGRA and TST tests, the overall prevalence of LTBI among HCWs was 40.98% (95% CI 34.77-47.33%). LTBI was associated with longer lengths of employment and exposure to patients, family members, or any person with TB. Additionally, older HCWs faced a higher risk of LTBI. Specific professional roles (such as nurses, nurse technicians, or physicians), smoking, and deficient TB infection control measures increased the likelihood of LTBI. However, information regarding gender and BCG vaccination status showed discordance among studies.
Conclusion: Our findings underscore a substantial burden of LTBI among HCWs in LAC countries. Implementing adequate infection control measures is essential to prevent and control transmission within healthcare settings.
Frequency and distribution of eschar in patients with scrub typhus in India: systematic review of literature and meta-analysis
Gupta Nitin,
Kumar Tirlangi Praveen,
Boodman Carl,
Fontaine Kim,
Bottieau Emmanuel,
Introduction. Scrub typhus is a mite-borne tropical febrile illness with high mortality if untreated. The presence of eschar is pathognomonic, but a wide range of frequencies of eschar positivity has been reported in Indian patients. Therefore, this systematic review and meta-analysis aimed to ascertain the frequency (overall and geographic region-wise) and anatomical distribution of eschar in scrub typhus in India.
Methodology. We searched articles in two databases using [(scrub OR typhus OR Orientia) AND (eschar) AND (India)]. The articles were independently screened and critically appraised by two authors. The frequency and distribution of eschar in patients with scrub typhus were pooled using a random-effect model.
Results. After the title-abstract and full-text screening, 107 articles (34002 cases of scrub typhus) were finally included. The overall pooled proportion of eschar positivity was 28.5% (95% CI: 24.1 to 32.9%). The pooled eschar positivity varied from <12% in Haryana, Rajasthan, Madhya Pradesh, Punjab, and Meghalaya to >46% in Tamil Nadu and Tripura. The pooled proportion of eschar positivity in the ‘trunk’ (39.3%), ‘groin’ (23.8%), and ‘axilla’ (16.5%) was higher than in the ‘limbs’ (9.9%) and ‘head’ (11.3%).
Conclusion. Eschar is reported in less than a third of the patients with scrub typhus in India. Most eschars were in the groin, axilla, and the trunk. There is a need to create awareness amongst physicians of the need for thorough physical examination
A perspective on the novel pentavalent Men5CV (NmCV-5) meningitis vaccine and Nigeria’s pioneering rollout campaign
Ukoaka Bonaventure Michael,
Okesanya Olalekan John,
Daniel Faithful Miebaka,
Affia Mmekom Obot,
Emeruwa Victoria Ezinne
The burden of meningitis poses great challenges for neurology and global health, manifesting with a range of symptoms from mild fever and headaches, to severe long term complications such as paralysis and cognitive impairment. Unfortunately, those living in endemic regions, especially survivors, are often confronted with the harsh reality of reduced quality of life as measured by disability-adjusted life years. Meningitis is one of the leading causes of mortality and morbidity, especially in the meningitis belt of sub-Saharan Africa, with a recorded disease burden of over 2.5 million cases globally and children under five disproportionately impacted. This paper examines the global burden of meningitis, exploring its prevalence and impact across different regions. It further analyzes the evolution of vaccination strategies for meningitis prevention, emphasizing the recent development and introduction of the novel Men5CV meningococcal conjugate vaccine. Recurrent meningitis outbreaks across the meningitis belt have resulted in significant mortality over decades. A major turning point in the fight against the serogroup A epidemic was the development of the MenAfriVac vaccine, which resulted in declining cases. However, serogroups C, W, and X continue to pose problems. The novel pentavalent (Men5CV) vaccine has emerged as a remarkable advancement in the fight against meningitis, with its safety and effectiveness against a variety of serogroups, including the elusive serogroup X, demonstrated in clinical trials. Its prequalification by the World Health Organization (WHO), and subsequent recommendation for incorporation into routine immunization programs issued a new era with the potential for meningitis eradication. Nigeria now sets a benchmark for other nations in the meningitis zone, becoming the first country in the world to roll out the new Men5CV vaccines. Funding from organizations like Gavi, the Vaccine Alliance, highlights the importance of coordinated international efforts aligned with the WHO's roadmap for meningitis elimination by 2030. Stakeholder involvement, extensive immunization campaigns, and a strong healthcare infrastructure are all practical recommendations for public health integration.
Original article
Early organism identification by Matrix Assisted Laser Desorption Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS) decreases the time to appropriate antibiotic modifications for common bacterial infections
Keri Vishakh C,
Gupta Ankesh,
Mohapatra Sarita,
Soneja Manish,
Kapil Arti,
Xess Immaculata,
Wig Naveet,
Kumar Bimal
Objective: MALDI-TOF-MS facilitates the identification of microorganisms from positive cultures in a timely and accurate manner. It eliminates the necessity for the application of biochemicals and operates on the principle of proteomics. It decreases the time required to report culture results. Prompt detection and notification of the pathogen, prior to the disclosure of antimicrobial susceptibilities, could potentially shorten the duration until the initial antibiotic adjustment is necessary, thereby influencing patients' clinical prognoses.
Methodology: Fifty patients in the conventional arm and one hundred patients in the interventional arm were compared in a pre and post quasi-experimental study conducted at a tertiary care centre in North India. Patients with positive cultures from medical wards and intensive care units were included. Comparing the time to first antibiotic modification after culture positivity, MALDI-TOF-MS-based identification, and clinical outcomes in both arms was the primary objective. Antibiotic modifications, escalation, and de-escalation were all recorded.
Results: The intervention arm exhibited a substantially shorter median time to first antibiotic modification (2010 mins vs 2905 mins, p=0.002) than the conventional arm. In the interventional group, a total of 44 out of 100 antibiotic modifications were implemented. Of these, 19 (43.3%) were determined solely by the MALDI report, without the anticipation of susceptibility assessments. De-escalation of antibiotics constituted the predominant form of modification (47.4%). The difference between the 27% and 32% mortality rates in the intervention arm and the conventional arm was not statistically significant (p=0.52).
Conclusion: MALDI-TOF-MS facilitates the modification of antibiotics early on. The primary benefit lies in the reduction of superfluous antibiotic usage. Early organism identification and reporting prior to the availability of susceptibility results did not result in any mortality benefit. This strategy, when combined with a strong antimicrobial stewardship programme, can aid in the reduction of antibiotic use
Microbial spectrum, management challenges, and outcome in patients with otogenic skull base osteomyelitis
AlSharhan Salma S,
Alwazzeh Marwan J,
ALRammah Mona K,
ALMarzouq Wasan F,
AlGhuneem Aishah A,
Alshrefy Afnan J,
Albahrani Nada A,
Telmesani Lena S,
A Ama,
Telmesani Laila M
Objectives: The study aimed to explore the spectrum and trend of causative microbial agents and to identify management challenges and the risk factors for poor outcomes in patients with confirmed otogenic skull base osteomyelitis. Methods: A retrospective observational study was conducted at a tertiary-care academic center from 1999 through 2019 and included 28 adult patients with confirmed otogenic skull base osteomyelitis. Relevant data was extracted from electronic and hard patient medical files. The microbial spectrum of involved microbes was identified and correlated to management options. Deterioration risk factors were investigated using suitable statistical analysis tests. Results: Twenty-eight patients with confirmed skull base osteomyelitis were included; most were males (78.6%) and Saudis (78.6%). All patients were ≥ 50 years of age (mean ± SD is 69.0 ±10.2.4). Of 41 identified microbial isolates, 56% were bacterial, 44% were fungal. 32.1% of patients had polymicrobial infections, most patients (92.8%) had received ≥ 2 systemic antibiotics, 57.1% received systemic antibiotic combinations, and 32.1% underwent surgical interventions. The mean antibiotic and antifungal therapy duration was 58.3 and 45.8 days, respectively. The identified risk factors of deterioration were advanced age and concomitant cardiac failure, with P-values of .006 and .034, respectively. Conclusions: The study findings highlight the microbiological spectrum and trend of otogenic skull base osteomyelitis-causative microbes over two decades, present the management challenges, identify deterioration risk factors, and suggest tissue biopsy as the golden standard for accurately identifying causative microbes.
Promoting molecular diagnostic equity: assessing in-house real-time PCR for Neisseria gonorrhoeae in anal samples from MSM recruited in an outpatient setting in Morocco.
Aitlhaj-mhand Rokaya,
Qasmaoui Aicha,
Bellaji Bahija,
Remz Chaimae,
Charof Reda,
El Jaoudi Rachid,
Abdelmoumen Hanaa,
Hançali Amina,
Oumzil Hicham
Objectives: Gonorrhea is a prevalent sexually transmitted infection among men who have sex with men (MSM). In Morocco, the basic laboratory diagnosis of Neisseria gonorrhoeae (NG) is based on microscopy and, in some settings, on culture. However, no nucleic acid amplification test (NAAT) has been implemented for routine diagnosis of gonorrhoeae.
The aim of this study is to assess the effectiveness of an in-house real-time PCR test for detecting N. gonorrhoeae DNA in anal swabs samples collected during an Integrated Behavioral and Biological survey. Patients and methods: Samples from 245 MSM, recruited using a Respondent Driven Sampling, were collected and tested for NG infection using GeneXpert CT/NG assay (Cepheid, USA). An In-House real-time PCR technique targeting the pseudo gene porA was developed and used for a parallel investigation of the same infection. The reliability of the in-house RT-PCR was validated through tests of reproducibility, repeatability, limit of detection, and cross-reactivity with other bacteria. The intrinsic performance characteristics of the qRT-PCR were assessed, namely, the sensitivity, the specificity, the positive predictive value (PPV), and the negative predictive value (NPV). The GeneXpert CT/NG assay was adopted as a reference method.
Results: For N. gonorrhoeae detection, the in-house real-time PCR assay showed a sensitivity and specificity of 80% and 100%, respectively. The PPV of the assay was 100% and the NPV was 97.3%. Conclusion: The in-house real-time PCR assay has high specificity and sensitivity, and it emerges as a promising approach for detecting N. gonorrhoeae in clinical specimens, particularly in decentralized settings such as regional laboratories.
Diagnostic role of CD64 expression on neutrophils as biomarker for blood stream infection in liver cirrhosis: some preliminary findings
Garlatti Costa Elena,
Venturini Sergio,
Colussi Gian Luca,
Pratesi Chiara,
Villalta Danilo,
Sabena Anna,
Grembiale Alessandro,
Pontoni Elisa,
Bramuzzo Igor,
Barbato Giuseppe,
Balbi Massimiliano,
Doretto Paolo,
Avolio Manuela,
Basaglia Giancarlo,
Crapis Massimo,
Tonizzo Maurizio,
Fagiuoli Stefano,
Grazioli Silvia
Background: The expression of CD64 on neutrophils (nCD64), measured using flow cytometry, has been proposed as a biomarker for bloodstream infections (BSI). However, data regarding its use in the setting of liver cirrhosis are lacking.
Methods: We compared nCD64 levels in 15 cirrhotic patients with BSI to those in 19 controls, including outpatients with stable decompensated cirrhosis without infection. Additionally, we compared nCD64 with C-reactive protein (CRP) and procalcitonin (PCT) in infected hospitalized cirrhotic patients.
Results: Cirrhotic patients with infection had higher levels of nCD64 compared to controls (6.0 [5.4-7.1] vs. 2.0 [1.5-2.2]; p<0.001). Among infected patients, a correlation between nCD64 (AUC=0.934 [0.875-0.982 95% CI]), CRP (AUC=0.972 [0.942-0.993 95% CI]), and PCT (AUC=0.859 [0.739-0.953 95% CI]) was observed. However, in our sample of cirrhotic individuals, nCD64 values were not significantly different between patients with worse prognosis and those with positive outcomes (p=0.448), and its expression was not influenced by Gram stain.
Conclusions: In our cohort, nCD64 appears to be a promising new biomarker for BSI. Additional prospective studies are needed to confirm its role and limitations in conjunction with other biomarkers and rapid microbiology in the diagnostic multidisciplinary pathway for septic cirrhotic patients.
Comparative Clinical Characteristics of Cytomegalovirus and Epstein-Barr Virus Mononucleosis in Immunocompetent Hosts: Experience from a Tropical Setting
Mohan Dheeraj,
Niyas Vettakkara Kandy Muhammed,
Arjun Rajalakshmi,
James Alan Francis
Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV) are herpesviruses that cause different clinical syndromes depending on the host's immune status. EBV is known for causing infectious mononucleosis (IMN), which presents with fever, pharyngitis, cervical lymphadenopathy, and atypical lymphocytes. CMV can also cause a mononucleosis syndrome with similar symptoms but is less frequently reported. Comparative studies on IMN and CMV mononucleosis from India are rare. This study aimed to elucidate the clinical characteristics of IMN and CMV mononucleosis in a South Indian tertiary care center, emphasizing the differences in their presentations. A retrospective analysis using Electronic Medical Records (EMR) from a tertiary care hospital at Thiruvananthapuram, Kerala, was conducted, including patients diagnosed with IMN or CMV mononucleosis based on clinical and serological tests during 2017 to 2023. Immunocompromised patients were excluded. The study compared demographic, clinical, and laboratory characteristics between the two groups. Out of 136 IMN cases and 17 CMV mononucleosis cases, the CMV group had a significantly higher median age (34.0 years) compared to the IMN group (20.0 years). The CMV group experienced a longer duration of fever (median 14.0 days) compared to the IMN group (5.0 days). Sore throat, cervical lymphadenopathy, and tonsil enlargement were significantly less common in CMV cases. The study concludes that CMV mononucleosis is more likely in older patients with prolonged fever and an absence of sore throat, tonsillitis, or cervical lymphadenopathy.
HCV testing and linkage to care for hepatitis C virus infection for marginalized drug user populations attending a harm reduction service in Bologna, Italy
Pavarin Raimondo Maria,
Badia Lorenzo,
Nisi Sebastiano,
Iormetti Claudia,
Caputo Fabio
Our aim was to estimate the prevalence of HCV in a highly vulnerable population of substance users living with social difficulties and marginality who came into contact with the mobile harm reduction service in the city of Bologna (Northern Italy).
Testing was offered in a van (mobile unit) by using a point-of-care HCV antibody test. For the HCV RNA test, the Xpert HCV Viral Load Fingerstick Test was used.
Participants with a detectable HCV RNA were accompanied within two weeks to the Infectious Diseases Department Sant’ Orsola Hospital Bologna to start HCV treatment.
With regard to the main study findings, 54% reported having never been HCV tested before; a prevalence of HCV RNA of 6% among all participants and 22% among those injecting drugs was found; among the HCV RNA positive participants, 80% were accompanied to treatment.
Our study suggests that mobile harm reduction services, in networks with healthcare facilities, are able to offer a continuous HCV screening service and linkage to care for people with drug use living in socially marginalized conditions.
Genetic variants of Nuclear Factor-Kappa B were associated with different outcomes of Hepatitis C virus infection among Egyptian patient
Gerges Marian,
Shora Hassan,
Abd-Elhamid Nahla,
Abdel-Kareem Alaa,
El-Nimr Sahar,
Badawy Ahmed,
Sharaf Ahmed,
El Gerby Manal,
Metwally Wafaa
Background: Hepatitis C virus (HCV) is a major risk factor for chronic hepatitis and hepatocellular carcinoma (HCC). Nuclear factor kappa B (NF-κB) is a transcription factor that functions in health and disease. Genetic variants of the NF-κB gene can affect its function and are associated with chronic inflammatory changes and malignant transformation. This case-control study is aimed to determine the possible association between NF-κB genetic variants and different outcomes of HCV infection among Egyptian patients. Subjects and Methods: 295 subjects were recruited with allocation of participants in the representative group according to results of serological and molecular tests. Patients in the case group (group A) were further divided into three subgroups; subgroup I, mild chronic HCV, subgroup II, cirrhosis, and subgroup III, HCC subgroups (59 for each subgroup), group B included participants who experienced spontaneous viral clearance (n=59). All were compared to matched healthy control subjects, Group C (n=59). All participants were genotyped for NF-κB polymorphisms, rs11820062 by TaqMan assay and rs28362491 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Risk analysis indicated that subjects carrying the rs11820062 A genotype are more susceptible to HCV infection (OR: 3.1; 95%, CI= 1.4-6.9). Subjects carrying the rs28362491 insertion genotype are at more risk of progression to cirrhosis when compared to healthy -controls and patients with mild chronic HCV (OR:7.7; 95% CI=2.4-24.3 and OR:5.1, 95% CI= 1.7-15.7, respectively) and also are at more risk of developing HCC when compared to healthy controls (OR:2.6; 95% CI= 0.94-7.3). Conclusion: Polymorphisms affecting NF-κB different genes would modulate HCV infection susceptibility and clinical disease progression among Egyptian patients.
The Infections in the History of Medicine
An examination of the influenza pandemic in early 20th century in Crete through the lens of the 1918 editions of Nea Ephimeris, a Cretan newspaper
Tsoucalas Gregory
Crete, strategically situated at the crossroads of three continents, was historically embroiled in incessant conflicts between colonisers and Greek revolutionaries, as well as recurrent battles against disease. In 1918, the island faced a novel adversary: influenza. In response, the state, local authorities, and medical professionals on the island mounted a formidable defence. Hospitals, health centres, and the military all contributed to the effort. Essential provisions of medicine and food were distributed to support the populations in areas most inflicted.
The Heraklion-based newspaper Nea Ephimeris played a crucial role in documenting these events. Through its articles, reports, interviews, and reviews of the influenza situation, it disseminated vital information that helped the public understand both preventive measures and the necessary actions to combat the spread of the virus. This study examines the coverage by Nea Ephimeris from January 1918 to January 1919, assessing how the newspaper informed, supported, and uplifted the urban and rural populations of Crete.
The data collected reconstruct the events of that period and demonstrate how historical pandemics offer lessons that can prepare health professionals for future challenges.
Unveiling Milan's hidden cases of plague occurred in autumn 1629, before the great 1630 epidemic
Nodari Riccardo,
Fois Luca,
Luconi Ester,
Vaglienti Folco,
Comandatore Francesco,
Galli Massimo
In the summer of 1630, Milan experienced the most devastating plague epidemic in its history. In this study, addressed to investigate the earliest phases of the epidemic in the autumn of 1629, a set of unpublished and only partially known primary sources produced by the city’s Officium Sanitatis was consulted and compared for the first time. Including those of two foreigners who died in the Lazzaretto, it was possible to ascertain a total of 39 cases of plague occurred in Milan between 9 October 1629 and the first weeks of 1630, of which 29 (74.4%) ended in death. Seven deaths presumably occurred at home were not recorded in the Liber Mortuorum, in which at least three other deaths caused by plague were deliberately attributed to a different cause. In particular, the case of the Vicario di Provisione in charge, Alfonso Visconti, probably the first death from plague occurred in Milan that year, was deliberately concealed for political reasons. Nevertheless, the spread of the disease remained limited in autumn 1629 and it was probably stopped until the following spring more by climatic factors than by the interventions of public health officials
Letters to the editor
First confirmed human case of H5N2 virus infection in Mexico: an emerging zoonotic concern
Apostolopoulos Vasso,
Sah Ranjit,
Mehta Rachana ,
Diaz Baruch,
Rodriguez-Morales Alfonso J.
not available