INTRODUCTION Vibrio cholerae is a microorganism that causes acute diarrheal diseases and cholera, one of the leading causes of global morbidity and mortality, especially in children under five years old. It is present in many regions and has been isolated from diverse sources such as water, soil and food. Surveillance of this microorganism in Cuba from 1985 through June 1997 showed circulation of non-epidemic non-O1/non-O139 serogroups, but surveillance continued to identify distribution of V. cholerae serotypes and serogroups in the different geographic regions of the country during the following years, due to the risk of introducing cholera-causing serogroups that provoked cholera epidemics in other countries of the region.

OBJECTIVES Describe the temporal‒spatial distribution of serogroups and serotypes of V. cholerae in Cuba.

METHODS A cross-sectional study was conducted that included isolates from passive surveillance of V. cholerae in 16 hygiene and epidemiology centers throughout Cuba from July 1997 through December 2019, submitted to the National Reference Laboratory for Acute Diarrheal Diseases of the Pedro Kourí Tropical Medicine Institute in Havana, Cuba. The timeline was subdivided into three five-year periods and one eight-year period. The centers submitting isolates were grouped into three geographical regions: western, central and eastern Cuba. A total of 1060 V. cholerae isolates were studied, from the 1438 samples sent from 15 Provincial Hygiene, Epidemiology and Microbiology Centers and the Municipal Hygiene, Epidemiology and Microbiology Center of the Isle of Youth Special Municipality. Genus, species and serotype of all specimens were studied and reviewed in the context of the outbreaks of acute diarrheal diseases reported in the country.

RESULTS All 1060 isolates were confirmed as V. cholerae. In the distribution by time period and region, the highest percentage occurred in the 2012‒2019 period, and the eastern region contributed the most isolates in all periods. Approximately 63.9% (677/1060) were from outbreaks, and in the 2012‒2019 period, the most epidemic-causing isolates came from the western region. Approximately 52.8% (560/1060) were identified as non-O1/non-O139 V. cholerae, and 47.2% (500/1060) as O1 V. cholerae; of these, 96.4% (482/500) corresponded to Ogawa serotype and 3.6% (18/500) to Inaba. Circulation of non-O1/non-O139 V. cholerae occurred throughout the entire period. The O1 serogroup began to circulate in 2012 and continued through 2016; however, since 2017, it has not been identified again. In the western region, there were smaller percentages of isolates of non-O1/non-O139 V. cholerae in all periods, except 2012‒2019. In that period, V. cholerae O1 was identified to a lesser degree in the central region.

CONCLUSIONS Vibrio cholerae circulated in all three Cuban regions during the years studied, with a higher percentage of isolates of the non-O1/non-O139 serogroup, which caused outbreaks or sporadic cases of diarrhea in the eastern region, with the exception of the 2012‒2019 period, when epidemic outbreaks of the O1 serogroup (which causes cholera) occurred in all three regions, with higher percentages in the western region.

KEYWORDS Vibrio cholerae; Vibrio cholerae O1; Vibrio cholerae non-O1; Vibrio cholerae O139; dysentery; cholera; epidemiological monitoring; infectious diarrheal disease; disease transmission, infectious; gastrointestinal diseases; Cuba

INTRODUCTION Polyserositis is described as inflammation with effusion of more than one serous membrane. There is very little published literature linking it to COVID-19 as a late complication.

OBJECTIVES Present and describe a case of post–COVID-19 polyserositis.

METHODS Data were collected from the medical record of a female patient admitted for fainting spells and marked weakness. The patient underwent a clinical evaluation, additional hematology, imaging and histopathology tests, and a surgical procedure.

The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor.

RESULTS We present the case of a 57-year-old female patient admitted to hospital for fainting spells and marked weakness, four months after COVID-19 infection. She also had a history of obesity, asthma, type 2 diabetes mellitus and a cholecystectomy in December 1992 for gallstones. Clinical assessment revealed pericardial effusion and bilateral pleural effusion, in addition to a tumor-like lesion outside the pericardium, proximal to the right ventricular wall. A surgical procedure and findings from additional tests led to diagnoses of thymic remnants and polyserositis.

CONCLUSIONS This is a case of polyserositis in a post–COVID-19 patient. After other causes of polyserositis were ruled out, and since there is a likely physiological and pathogenic mechanism operating between the two diseases, the polyserositis was determined to be a late complication of COVID-19. To date, it is the second case reported in the world and the first reported in Cuba.

KEYWORDS COVID-19, SARS-CoV-2, colchicine, pericardial effusion, pleural effusion, pericarditis, thoracoscopy, Cuba

INTRODUCTION In inflammatory respiratory diseases, the imbalance between proteases and endogenous protease inhibitors leads to an exacerbated activity of human neutrophil elastase (a protease that destroys the extracellular matrix and stimulates proinflammatory cytokine release). Elastase is considered a target in the search for therapeutic treatments for inflammatory respiratory diseases. Pulmonary surfactant is a promising product for this purpose, because in addition to its biophysical function, it has anti-inflammatory properties.

OBJECTIVES Evaluate effect of the Cuban porcine pulmonary surfactant (Surfacen), the rCmPI-II elastase inhibitor, and the Surfacen/rCmPI-II combination on activated neutrophil elastase activity in vitro, and determine if Surfacen’s interface property changes in the presence of the inhibitor.

METHODS The anti-elastase effect of Surfacen, rCmPI-II and the Surfacen/rCmPI-II combination was evaluated in an in vitro model of activated neutrophils, previously purified from the blood of healthy subjects. The cells were stimulated with LPS/fMLP and were incubated with different concentrations of Surfacen, rCmPI-II and the Surfacen/rCmPI-II combination. Elastase activity was measured. The interface property was determined on a Langmuir surface balance.

The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor.

RESULTS Surfacen at 10 mg/mL inhibited 71% of stimulated neutrophil elastase activity. rCmPI-II at 0.1 μM reduced 20% of elastase activity; at 200 μM—the maximum concentration evaluated—inhibition was 68%. Both products had a dose-dependent effect. The Surfacen/inhibitor combination (0.5 mg/mL/80 µM) did not affect the surfactant interface property or the inhibitory activity of rCmPI-II against human neutrophil elastase.

CONCLUSIONS Surfacen and the rCmPI-II inhibitor have an anti-elastase effect on an activated neutrophil model. rCmPI-II does not affect Surfacen’s interface property and, therefore, both can be evaluated for combined use in treating inflammatory lung diseases.

KEYWORDS Pulmonary surfactants, elastase inhibitor, drug carriers, neutrophils, Cuba

INTRODUCTION Bile acids are signaling molecules with immune, metabolic and intestinal microbiota control actions. In high serum concentrations they increase inflammatory response from the liver-gut axis, until causing multiorgan failure and death; therefore, they may be associated with COVID-19’s clinical progression, as a consequence of tissue and metabolic damage caused by SARS-CoV-2. While this topic is of considerable clinical interest, to our knowledge, it has not been studied in Cuba.

OBJECTIVES Study and preliminarily characterize patients admitted with a diagnosis of COVID-19 and high levels of serum bile acids.

METHODS A preliminary exploratory study was carried out with descriptive statistical techniques in 28 COVID-19 patients (17 women, 11 men; aged 19–92 years) who exhibited high levels of serum bile acids (≥10.1 µmol/L) on admission to the Dr. Luis Díaz Soto Central Military Hospital in Havana, Cuba, from September through November 2021.

RESULTS On admission patients presented hypocholesterolemia (13/28; 46.4%), hyperglycemia (12/28; 43.0%) and hyper gamma-glutamyl transpeptidase (23/28; 84.2%). Median blood glucose (5.8 mmol/L) and cholesterol (4.1 mmol/L) were within normal ranges (3.2‒6.2 mmol/L and 3.9‒5.2 mmol/L, respectively). Severe or critical stage was the most frequent (13/28) and median serum bile acids (31.6 µmol/L) and gamma-glutamyl transferase (108.6 U/L) averaged well above their respective normal ranges (serum bile acids: 0‒10 µmol/L; GGT: 9‒36 U/L). Arterial hypertension was the most frequent comorbidity (19/28; 67.9%).

CONCLUSIONS Severe or critical stage predominated, with serum bile acids and gamma-glutamyl transferase blood levels above normal ranges. The study suggests that serum bile acid is toxic at levels ≥10.1 µmol/L, and at such levels is involved in the inflammatory process and in progression to severe and critical clinical stages of the disease. In turn, this indicates the importance of monitoring bile acid homeostasis in hospitalized COVID-19 patients and including control of its toxicity in treatment protocols.

KEYWORDS COVID-19, SARS-CoV-2, bile acids and salts, gamma-glutamyl transferase, pregnant women, postpartum, Cuba

The COVID-19 pandemic has caused notable changes in all areas of our lives. Pandemic-coping strategies include attention and care at various levels, for different people and in various scenarios. Death is one of the most feared consequences of COVID-19 for both patients and their families; for the latter, the grief and adaptation processes to loss require that care for grievers be an important part of the public health response to the COVID-19 pandemic.

Grief from losses due to COVID-19 has distinctive features: it is not anticipatory (with virtually no time or progressive stages to facilitate adaptation to loss); closure or goodbyes are not possible (in-person social support decreases due to distancing to minimize risk of infection); it may affect various close relationships (a relevant predictor of complicated grief); it may imply stigmatization by peers, friends and neighbors; it is preceded by a period of absence of fluid and in-person communication between family members and the hospitalized patient; and those who break the news of the death are often professionals in red zones who are stressed and do not always have the skills or the ability to properly communicate bad news.

The death of a family member from COVID-19 generally causes an unexpected crisis in the family, which is already affected by the pandemic and its daily consequences. This has prompted an analysis of COVID-19 loss on family life and how best to mitigate its consequences.

During the COVID-19 pandemic, care and monitoring of the grief of family members and those who were close to the deceased require psychological action within a framework of comprehensive care, which demands preparation of healthcare professionals. Experiences described are taken from some actions developed in Cuba.

KEYWORDS Grief, psychology, death, attitude to death, COVID-19, SARS-CoV-2, Cuba

INTRODUCTION Ferritin is the best biomarker for assessing iron deficiency, but ferritin concentrations increase with inflammation. Several adjustment methods have been proposed to account for inflammation’s effect on iron biomarker interpretation. The most recent and highly recommended method uses linear regression models, but more research is needed on other models that may better define iron status in children, particularly when distributions are heterogenous and in contexts where the effect of inflammation on ferritin is not linear.

OBJECTIVES Assess the utility and relevance of quadratic regression models and quantile quadratic regression models in adjusting ferritin concentration in the presence of inflammation.

METHODS We used data from children aged under five years, taken from Cuba’s national anemia and iron deficiency survey, which was carried out from 2015–2018 by the National Hygiene, Epidemiology and Microbiology Institute. We included data from 1375 children aged 6 to 59 months and collected ferritin concentrations and two biomarkers for inflammation: C-reactive protein and α-1 acid glycoprotein. Quadratic regression and quantile regression models were used to adjust for changes in ferritin concentration in the presence of inflammation.

RESULTS Unadjusted iron deficiency prevalence was 23% (316/1375). Inflammation-adjusted ferritin values increased iron-deficiency prevalence by 2.6–4.5 percentage points when quadratic regression correction model was used, and by 2.8–6.2 when quantile regression was used. The increase when using the quantile regression correction model was more pronounced and statistically significant when both inflammation biomarkers were considered, but adjusted prevalence was similar between the two correction methods when only one biomarker was analyzed.

CONCLUSIONS The use of quadratic regression and quantile quadratic regression models is a complementary strategy in adjusting ferritin for inflammation, and is preferable to standard regression analysis when the linear model’s basic assumptions are not met, or when it can be assumed that ferritin–inflammation relationships within a subpopulation may deviate from average trends.

KEYWORDS Alpha-1-acid glycoprotein, C-reactive protein, anemia, iron deficiency, ferritin, acute phase protein, Cuba

INTRODUCTION COVID-19 sequelae, or the short-, medium-, and long-term manifestations of the disease are under continuous study. There are currently few reports on the evolution of hematological variables following a demonstrated absence of SARS-CoV-2 after infection.

OBJECTIVE Identify hematological alterations in Cuban adults recovered from SARS-CoV-2 infection, and their relation with disease severity.

METHODS We selected 348 persons recovered from COVID-19 residing in Havana, Cuba with an RT-PCR study negative for SARS-CoV-2 performed two weeks after hospital discharge; a structured survey was administered to obtain clinical–epidemiological data. Three groups were established according to COVID-19 clinical criteria: asymptomatic, mild/moderately symptomatic, and severely symptomatic, which, in turn, were divided according to hospital discharge date and blood sample collection date. We performed hemograms with differential leukocyte counts and compared results among groups. We then measured the associations between hematological variables, personal medical history, and relevant lifestyle habits (smoking).

RESULTS All hematological variables were within normal reference limits, although men from the group of severely ill patients had increased total leukocytes, neutrophils and lymphocytes, and decreased hemoglobin and eosinophils, which was also evident in those with a recovery time of 31–90 days.

CONCLUSIONS The relation between hematological variables and degree of clinical severity offers evidence as to persistence of systemic alterations (possibly inflammatory) associated with viral infection. Their identification and characterization can facilitate personalized patient followup and rehabilitation.

KEYWORDS COVID-19, SARS-CoV-2, hematology, leukocytosis, neutrophils, eosinophils, Cuba

INTRODUCTION Immunity in cancer patients is modified both by the cancer itself and by oncospecific treatments. Whether a patient’s adaptive immunity is impaired depends on their levels of naive lymphocytes and other cell populations. During the COVID-19 pandemic, cancer patients are at greater risk of progressing to severe forms of the disease and have higher mortality rates than individuals without cancer, particularly while they are receiving cancer-specific therapies. An individual’s protection against infection, their response to vaccines, and even the tests that determine the humoral immune response to SARS-CoV-2, depend on lymphocyte populations, meriting their study.

OBJECTIVE Estimate blood concentrations of lymphocytes involved in the immune response to new pathogens in cancer patients.

METHODS We carried out an analytical study of 218 cancer patients; 124 women and 94 men, 26–93 years of age, who were treated at the National Oncology and Radiobiology Institute in Havana, Cuba, March–June, 2020. Patients were divided into five groups: (1) those with controlled disease who were not undergoing cancer-specific treatment; (2) those undergoing debulking surgery; (3) patients undergoing chemotherapy; (4) patients undergoing radiation therapy and (5) patients currently battling infection. We evaluated the following peripheral blood lymphocyte subpopulations via flow cytometry: B lymphocytes (total, naive, transitional, memory, plasmablasts and plasma cells); T lymphocytes (total, helper, cytotoxic and their respective naive, activated, central memory and effector memory subsets); and total, secretory and cytotoxic natural killer cells and T natural killer cells. We also estimated neutrophil/lymphocyte ratios. Lymphocyte concentrations were associated with controlled disease and standard cancer therapy. For variables that did not fall within a normal distribution, ranges were set by medians and 2.5–97.5 percentiles. The two-tailed Mann–Whitney U test was used to measure the effect of sex and to compare lymphocyte subsets. We calculated odds ratios to estimate lymphopenia risk.

RESULTS All cancer patients had lower values of naive helper and cytotoxic T lymphocyte populations, naive B lymphocytes, and natural killer cells than normal reference medians. Naive helper T cells were the most affected subpopulation. Memory B cells, plasmablasts, plasma cells, activated T helper cells, and cytotoxic central memory T cells were increased. Patients undergoing treatment had lower levels of naive lymphocytes than untreated patients, particularly during radiation therapy. The risk of B lymphopenia was higher in patients in treatment. The odds ratio for B lymphopenia was 8.0 in patients who underwent surgery, 12.9 in those undergoing chemotherapy, and 13.9 in patients in radiotherapy.

CONCLUSIONS Cancer and conventional cancer therapies significantly affect peripheral blood B lymphocyte levels, particularly transitional T helper lymphocytes, reducing the immune system’s ability to trigger primary immune responses against new antigens.

KEYWORDS Cancer, lymphocyte subsets, flow cytometry, immunity, virus diseases, Cuba

INTRODUCTION Urinary tract infection is the second-leading reason for consults in primary health care. Bacterial urinary tract infections are the most common, of which Escherichia coli is the main etiologic agent. Antimicrobial resistance and multidrug resistance complicate effective community treatment, especially if resistance is caused by extended-spectrum beta-lactamase production. WHO recommends that antimicrobial susceptibility be evaluated in different regions of the world at different times. Community-acquired E. coli’s susceptibility to colistin has not yet been studied in Cuba, and mcr-1 gene screening is necessary.

OBJECTIVE Evaluate community-acquired uropathogenic E. coli isolates’ susceptibility to antibiotics, including colistin, and identify extended-spectrum beta-lactamase–producing bacteria.

METHODS We conducted a descriptive cross-sectional study that included 281 community-acquired uropathogenic E. coli isolates (153 from the Isle of Youth Special Municipality’s Hygiene, Epidemiology, and Microbiology Center and 128 from Microbiology Laboratories of 7 institutions in Havana) from June 2016 through July 2018. We used the disk diffusion method to determine susceptibility to ampicillin, ampicillin/sulbactam, cefazolin, trimethoprim/sulfamethoxazole, ciprofloxacin, nitrofurantoin and fosfomycin. The disk elution method was used to determine susceptibility to colistin. The combined disk method was used to identify extended-spectrum beta-lactamases. Estimates were made regarding the frequency and percentages of antimicrobial susceptibility and resistance, as well as multidrug-resistance patterns.

RESULTS Of the 281 isolates, 68.3% (192/281) were resistant to ampicillin, 54.8% (154/281) were resistant to ciprofloxacin, and 49.5% (139/281) were resistant to trimethoprim/sulfamethoxazole. Resistance to colistin was not detected. On the other hand, 14.2% (40/281) were susceptible to the 8 antibiotics we evaluated, 22.1% (62/281) showed resistance to only 1 antibiotic, and 63.7% (179/281) were resistant to 2 or more antibiotics. In the extended-spectrum beta-lactamase determination, 34.5% (97/281) had inhibition zones ≤14 mm with cefazolin. Of those with inhibition zones, 64.9% (63/97) were positive in the phenotype test, and 35.1% (34/97) were negative. In extended-spectrum beta-lactamase–producing bacteria, 1.6% (1/63) were resistant to fosfomycin, and 3.2% (2/63) were resistant to nitrofurantoin. The most common multidrug-resistance pattern (22.9%; 30/131) was to ampicillin/sulbactam, ampicillin, cefazolin, ciprofloxacin, and trimethoprim/sulfamethoxazole.

CONCLUSIONS Uropathogenic E. coli resistance to the antibiotics most frequently used in community medical practice is quite common, and extended-spectrum beta-lactamase–producing bacteria is the mechanism for beta-lactam antibiotic resistance. Multidrug-resistance patterns include resistance to the antibiotics most used in community-acquired infections. Fosfomycin and nitrofurantoin are the most active in extended-spectrum beta-lactamase producing bacteria. All the isolates were susceptible to colistin.

KEYWORDS Uropathogenic Escherichia coli, urinary tract infections, microbial susceptibility tests, Cuba

INTRODUCTION The use of various diagnostic techniques is increasingly common in pandemic scenarios. It is important to update evaluations of their metric properties in different times and settings.

OBJECTIVE Evaluate metric properties of a SARS-CoV-2 rapid antigen test relative to a reference standard.

METHODS We carried out a prospective evaluation study of the SARS-CoV-2 rapid antigen test as compared to the RT-PCR test, which is considered the reference standard. Our sample was comprised of 778 individuals, and we calculated sensitivity, specificity, predictive values, prevalence and validity indices.

RESULTS Of the total 778 samples, 70 were true positives, 658 were true negatives, and 27 were false negatives when compared to RT-PCR test results. We obtained a sensitivity of 75.3% (95% CI = 65.96–84.50); a specificity of 96.1% (95% CI = 94.53–97.59); 72.2% for positive predictive value, and 96.6% for negative predictive value. The estimated prevalence was 11.9% and the validity index was 93.6%.

CONCLUSIONS The index values validate use of the SARS- CoV-2 rapid antigen test until prevalence falls below 2.5%, since as SARS-CoV-2 infection prevalence decreases, so does the predictive value of the PCR result.

The use of the SARS-CoV-2 rapid antigen test on the Isle of Youth, Cuba, was decisive in the pandemic’s clinical– epidemiological management.

KEYWORDS SARS-CoV-2, COVID-19, antigens, validation study, sensitivity and specificity, Cuba

Cuba’s decision in September 2021 to launch a massive vaccination campaign against COVID-19 for children as young as two years old turned heads around the world—of clinicians, immunologists, public health experts, governments and regulatory authorities alike. Since then—and just as pediatric COVID-19 hospitalizations reached record numbers globally—some two million Cuban children and adolescents have received the Cuban Soberana vaccines (1.7 million, or 81.3% of that population through December 16, 2021).[1]

Why did Cuban health authorities decide to vaccinate children? What clinical trials provided the evidence for such a course of action, especially for the youngest? And what have been the results thus far?

To answer these and other questions, MEDICC Review spoke with Dr Rinaldo Puga, principal investigator for the completed phase 1/2 clinical trials of the Finlay Vaccine Institute’s Soberana 02 and Soberana Plus vaccines in pediatric ages. Dr Puga’s 30 years as a practicing pediatrician have been accompanied by teaching and research, the latter earning him awards from the Cuban Academy of Sciences, among others. He is currently chief of pediatrics and chair of the Scientific Council at the Cira García Clinic in Havana, which granted him leave to lead the pediatric vaccine trials.

As 2021 drew to a close, Cuba struggled to contain the highly transmissible omicron variant of SARS-CoV-2, braced for a new wave of infections and kept a close eye on other variants of concern popping up around the world—a common experience to countries everywhere as we head into the second year of the pandemic. In Cuba, however, there is one marked difference making all the difference: by early January, 87% of the population was fully vaccinated using a three-dose schedule of vaccines developed and produced on the island.[1] This massive vaccination campaign is complemented by a rapid booster rollout—also using Cuban vaccines—that began in December 2021 and was ongoing as we finalized this issue.

The island nation was able to achieve the third highest COVID-19 vaccination rate in the world[2] after decades of scientific investment, research, discovery and innovation; regulatory oversight and compliance; professional training; and increased production capacity. But a vaccine is only as effective as the health system charged with administering it—in a safe and timely manner, to as many people as possible. Here too, Cuba has decades of experience, including a national pediatric immunization program where 98% of children under 5 are immunized against 13 diseases,[3] an annual polio vaccination campaign (both launched in 1962 and uninterrupted since) and campaigns to contain epidemics such as H1N1.

When the first COVID-19 cases were detected on the island in March 2020, Cuba harnessed this vaccine experience, making a hard tack towards developing its own vaccines. Two of the main protagonists in the country’s biotechnology development, the Finlay Vaccine Institute (IFV) and the Genetic Engineering and Biotechnology Center (CIGB), both with several groundbreaking preventive and therapeutic vaccines in their portfolios, led the search for a vaccine. Today, Cuba has three vaccines authorized for emergency use—Soberana 02 and Soberana Plus developed by IFV, and Abdala, developed by CIGB. Schedules with these vaccines have demonstrated more than 90% efficacy in clinical trials,[4] and after regulatory approval for emergency use, became the backbone of Cuban COVID-19 vaccination efforts. A fourth vaccine, Mambisa (CIGB), administered nasally, and a fifth, Soberana 01 (IFV) are still in clinical trials.

For this installment in MEDICC Review’s series spotlighting leading women of Cuban science, we sat down with Dr Verena Muzio, Director of Clinical Research at CIGB. A pioneer of Cuba’s biotechnology sector, she is an immunologist with a doctorate in biological sciences. Her professional trajectory began researching the genetically engineered hepatitis B surface antigen that led to the development of Cuba’s recombinant hepatitis B vaccine in 1989. The same technological platform used in this vaccine was used to develop CIGB’s Abdala vaccine against SARS-CoV-2—part of the reason Cuba was able to secure a vaccine so quickly. A phase 3 clinical trial determined a 92.28% efficacy rate for Abdala, with results to appear in forthcoming publications.