An uncontrolled clinical trial carried out in Panama City, Panama.
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Global diversity and evolution of Salmonella enterica serovar Panama: a genomic epidemiology study.
BACKGROUND: Non-typhoidal Salmonella is a globally important bacterial pathogen, typically associated with foodborne gastrointestinal infection. Some non-typhoidal Salmonella serovars can also colonise typically sterile sites in people to cause invasive non-typhoidal Salmonella disease. Salmonella enterica serovar Panama is responsible for a substantial number of cases of human bloodstream infection, but despite its global dissemination, numerous outbreaks, and a reported association with invasive non-typhoidal Salmonella disease, S enterica serovar Panama (S Panama) is understudied. We aimed to describe the genomic epidemiology and evolutionary history of S Panama to provide a vital baseline of understanding for this globally important serovar. METHODS: In this genomic epidemiology study, we analysed S Panama genomes derived from historical collections, national surveillance datasets, and publicly available epidemiological and whole-genome sequencing data which span the years 1931-2019. Maximum likelihood and Bayesian phylodynamic approaches were used to investigate population structure and evolutionary history and to infer geotemporal dissemination. A combination of different bioinformatic approaches with short-read and long-read data were used to characterise geographical and clade-specific trends in antimicrobial resistance (AMR) and genetic markers for invasiveness. FINDINGS: We analysed 836 S Panama genomes, of which 559 (67%) were sequenced as part of this study. The collection represents all inhabited continents and includes isolates collected between 1931 and 2019. We identified the presence of four geographically linked S Panama clades (C1 [ie, the Latin America and the Caribbean clade; n=338], C2 [ie, the European clade; n=124], C3 [ie, the Martinique clade; n=131], and C4 [ie, the Asia and Oceania clade; n=104]) and regional trends in AMR profiles. Most isolates (715 [86%] of 836) were pan-susceptible to antibiotics and belonged to clades circulating in Latin America and the Caribbean (64%, n=458). Most antibiotic-resistant isolates in our collection (113 [93%] of 121) fell within clades C4 (ie, the Asia and Oceania clade) and C2 (ie, the European clade), the latter of which had the highest invasiveness index values based on the conservation of 196 extraintestinal predictor genes. INTERPRETATION: This first large-scale phylogenetic analysis of S Panama has revealed important information about the population structure, AMR, global ecology, and genetic markers of invasiveness of the identified genomic subtypes. Our findings provide an important baseline for understanding S Panama infection. The presence of multidrug-resistant clades with elevated invasiveness index values should be monitored through ongoing surveillance, as such clades could pose an increased public health risk. FUNDING: UK Research and Innovation Global Challenges Research Fund and Biotechnology and Biological Sciences Research Council, UK Medical Research Council, Wellcome Trust, John Lennon Memorial Scholarship, Institut Pasteur, Santé publique France, Fondation Le Roch-Les Mousquetaires, Investissement d'Avenir Programme, and Australian National Health and Medical Research Council.
Humans↗
An ecosystem report on the Panama Canal: monitoring the status of the forest communities and the watershed.
In 1996, the Smithsonian Tropical Research Institute and the Republic of Panama's Environmental Authority, with support from the United States Agency for International Development, undertook a comprehensive program to monitor the ecosystem of the Panama Canal watershed. The goals were to establish baseline indicators for the integrity of forest communities and rivers. Based on satellite image classification and ground surveys, the 2790 km2 watershed had 1570 km2 of forest in 1997, 1080 km2 of which was in national parks and nature monuments. Most of the 490 km2 of forest not currently in protected areas lies along the west bank of the Canal, and its management status after the year 2000 turnover of the Canal from the U.S. to Panama remains uncertain. In forest plots designed to monitor forest diversity and change, a total of 963 woody plant species were identified and mapped. We estimate there are a total of 850-1000 woody species in forests of the Canal corridor. Forests of the wetter upper reaches of the watershed are distinct in species composition from the Canal corridor, and have considerably higher diversity and many unknown species. These remote areas are extensively forested, poorly explored, and harbor an estimated 1400-2200 woody species. Vertebrate monitoring programs were also initiated, focusing on species threatened by hunting and forest fragmentation. Large mammals are heavily hunted in most forests of Canal corridor, and there was clear evidence that mammal density is greatly reduced in hunted areas and that this affects seed predation and dispersal. The human population of the watershed was 113 000 in 1990, and grew by nearly 4% per year from 1980 to 1990. Much of this growth was in a small region of the watershed on the outskirts of Panama City, but even rural areas, including villages near and within national parks, grew by 2% per year. There is no sewage treatment in the watershed, and many towns have no trash collection, thus streams near large towns are heavily polluted. Analyses of sediment loads in rivers throughout the watershed did not indicate that erosion has been increasing as a result of deforestation, rather, erosion seems to be driven largely by total rainfall and heavy rainfall events that cause landslides. Still, models suggest that large-scale deforestation would increase landslide frequency, and failure to detect increases in erosion could be due to the gradual deforestation rate and the short time period over which data are available. A study of runoff showed deforestation increased the amount of water from rainfall that passed directly into streams. As a result, dry season flow was reduced in a deforested catchment relative to a forested one. Currently, the Panama Canal watershed has extensive forest areas and streams relatively unaffected by humans. But impacts of hunting and pollution near towns are clear, and the burgeoning population will exacerbate these impacts in the next few decades. Changes in policies regarding forest protection and pollution control are necessary.
Animals↗
Cervical cancer in the Republic of Panama.
Cervical cancer is more common in Latin America than elsewhere in the world. Previous work indicated that Panama also had a high incidence of cervical cancer and that the disease clustered in rural Herrera Province; to document this and collect detailed information on risk factors, the authors established a population-based Cervical Cancer Registry in Panama. Cervical cancer cases diagnosed between 1974 and 1979 were identified by visiting every major hospital in the country. The registry abstracted epidemiologic, clinical, and other information from patients' hospital charts. It recorded an age-adjusted invasive cervical cancer incidence of 28.4/100,000 between 1974 and 1979; rural Herrera Province supported the highest rate (79.1/100,000), while urban Panama Province had a low rate (24.6/100,000); in situ disease followed a similar pattern (48.7/100,000 in Herrera Province and 17.6/100,000 in Panama Province). Women born in Herrera Province retained high cervical cancer rates irrespective of residence at diagnosis (64.7/100,000), while women from Panama Province had low rates (12.4/100,000) which were comparable to those seen in US whites. In addition to having high cancer rates, women from Herrera Province developed invasive disease at an unusually young age; women between 35 and 39 years of age had an incidence of 151/100,000.
Adolescent↗
Assessing the reliability and validity of a residency selection process examination: a preliminary study between the national board of medical examiners and the University of Panama Faculty of Medicine.
BACKGROUND: The Ministry of Health of the Republic of Panama is currently developing a national examination system that will be used to license graduates to practice medicine in that country, as well as to undertake postgraduate medical training. As part of these efforts, a preliminary project was undertaken between the National Board of Medical Examiners (NBME) and the Faculty of Medicine of the University of Panama to develop a Residency Selection Process Examination (RSPE). PURPOSE: The purpose of this study was to assess the reliability and validity of RSPE scores for a sample of candidates who wished to obtain a residency slot in Panama. METHODS: The RSPE, composed of 200 basic and clinical sciences multiple-choice items, was administered to 261 residency applicants at the University of Panama. RESULTS: The reliability estimate computed was comparable with that reported with other high-stakes examinations (Cronbach's alpha = 0.89). Also, a Rasch examinee proficiency item difficulty plot showed that the RSPE was well targeted to the proficiency levels of candidates. Finally, a moderate correlation was noted between local grade point averages and RSPE scores for University of Panama students (r = 0.38). CONCLUSIONS: Findings suggest that it is possible to translate and adapt test materials for use in other contexts.
Internship and Residency↗
Enteritis due to Salmonella panama from infected ham.
After the appearance of sporadic cases of enteritis due to Salmonella panama, baked ham from one supplier was implicated as the source of infection. No pathogenic organisms were isolated from the working surfaces of the factory involved or from samples of a day's bacon output, but S. panama was isolated from the factory sewers. Stool examinations of the 500 employees showed one man in the baked ham section to be excreting S. panama. He was removed from work and no further infections were reported from the district. The organism could no longer be found in the sewers.Some weeks later, further infections were reported in the London and Southend areas, which could be traced to ham from the original source. Sewer swabs at the factory were again positive. A further examination of all the employees revealed three cases and 82 symptomless excretors. Eight of 192 family contacts were also found to be excretors. Trimethoprim-sulphamethoxazole appeared to have no effect on the carrier state.Examination of the hams in cold store showed some to be infected with S. panama, and a number of these had been consumed in the canteen.Subsequent examination of pigs at slaughter and pig food prepared locally failed to isolate S. panama. The source of infection at the factory is unknown.
Animal Feed↗
Drug utilization in Panama.
The availability and use of therapeutic agents in Panama is critically reviewed. Of the 3800 drug products on the market, 50% are vitamins, tonics and fixed ratio combination products. Many drugs are of unproven efficacy and safety, not marketed in more developed countries. Hospital and outpatient studies have documented inappropriate prescribing habits. To improve drug utilization, regulatory and educational strategies have been implemented in the Panama Social Security Institute. Drugs of doubtful or no value and unnecessary duplications have been withdrawn from its therapeutic formulatory. Outreach services provided by the Panama Social Security Institute include the distribution of a drug bulletin, workshops, seminars and person to person drug information (counterdetailing) to health personnel. Drug information to patients is also included in the overall strategy to promote the rational use of drugs. Nevertheless, much work is still needed to formulate and implement an essential drugs and health policy in Panama.
Drug Utilization↗
Human immunodeficiency virus infection in the Republic of Panama.
Thirty-one documented acquired immune deficiency syndrome (AIDS) cases occurred in Panama during 1984-1987. Twenty-three (74%) patients were homosexual males and all but 2 patients recognized prior to June 1987 have died. To identify risk factors for human immunodeficiency virus infection, 287 male homosexual residents of Panama City were enrolled in a cross-sectional study. Nine had human immunodeficiency virus (HIV) antibody. Travel to the United States, homosexual relations with United States nationals in Panama, and sexual contacts in Panamanian clubs and bars were associated with human immunodeficiency virus infection by logistic regression analysis. Number of different male sex partners per year was identified but did not enter the logistic model at a significant level. To estimate seroprevalence in other high risk populations, 183 Panama City female prostitutes and 55 homosexual males from the rural Azuero peninsula were screened; none were seropositive. Eighty-four percent of Panamanian hemophiliacs had antibody; infection was related to factor VIII transfusions. Two of 182 sickle cell anemia patients and 15 of 7,720 volunteer blood donors were positive.
Acquired Immunodeficiency Syndrome↗
[Current situation of the Aedes aegypti mosquito in the metropolitan area of Panama city].
Ae. aegypti was reintroduced into Panama in 1985; control was unsuccessful and by 1988 Ae. aegypti larvae were detected in every borough of Panama Metropolitan Area. Only 3% of the Panama City population has dengue antibody (against DEN 2) and virtually no one is immune to other serotypes. The relative risk of the introduction of Dengue virus into Panama is discussed.
Aedes↗
Multiple evolutionary origins of the fungus causing Panama disease of banana: concordant evidence from nuclear and mitochondrial gene genealogies.
Panama disease of banana, caused by the fungus Fusarium oxysporum f. sp. cubense, is a serious constraint both to the commercial production of banana and cultivation for subsistence agriculture. Previous work has indicated that F. oxysporum f. sp. cubense consists of several clonal lineages that may be genetically distant. In this study we tested whether lineages of the Panama disease pathogen have a monophyletic origin by comparing DNA sequences of nuclear and mitochondrial genes. DNA sequences were obtained for translation elongation factor 1alpha and the mitochondrial small subunit ribosomal RNA genes for F. oxysporum strains from banana, pathogenic strains from other hosts and putatively nonpathogenic isolates of F. oxysporum. Cladograms for the two genes were highly concordant and a partition-homogeneity test indicated the two datasets could be combined. The tree inferred from the combined dataset resolved five lineages corresponding to "F. oxysporum f. sp. cubense" with a large dichotomy between two taxa represented by strains most commonly isolated from bananas with Panama disease. The results also demonstrate that the latter two taxa have significantly different chromosome numbers. F. oxysporum isolates collected as nonpathogenic or pathogenic to other hosts that have very similar or identical elongation factor 1alpha and mitochondrial small subunit genotypes as banana pathogens were shown to cause little or no disease on banana. Taken together, these results indicate Panama disease of banana is caused by fungi with independent evolutionary origins.
Base Sequence↗
Evolution of drug resistance in Salmonella panama isolates in Chile.
In a search for Salmonella isolates in the environment in Chile in 1975, drug-susceptible strains of Salmonella panama were recovered for the first time from river water and vegetables in the vicinity of Santiago. Two to 3 years later, antibiotic-resistant S. panama began to appear in a variety of sources (meat, animals, vegetables, etc.), giving rise to a human epidemic that involved the entire nation. Of 139 clinical isolates studied, 7 were drug susceptible, 11 were resistant only to nitrofurans, and 3 were streptomycin, spectinomycin, and nitrofuran resistant; none of these 21 isolates harbored plasmid DNA. Most isolates (n = 107) were resistant to nitrofurans (chromosomal) and to streptomycin, spectinomycin, sulfonamides, tetracycline, and mercuric and tellurite salts; this multidrug resistance was encoded on a 218-kb plasmid classified in a number of strains as being in the IncHI2 group. From 1982 to 1993, 11 isolates acquired an additional self-transferable plasmid coding for resistance to any one of ampicillin (61 kb), ampicillin and trimethoprim (65 kb), ampicillin, trimethoprim, streptomycin, and sulfonamides (71 kb), ampicillin, gentamicin, kanamycin, and tetracycline (120 kb), or a nontransferable plasmid of approximately 6 kb encoding resistance to ampicillin or kanamycin. With the exception of ampicillin or ampicillin and trimethoprim resistance, S. panama isolates from foodstuffs, mainly pork meat products, and animals had resistance patterns that were the same as those found in clinical specimens. Remarkably, strains from goats and goat cheese and from shellfish isolated in particular rural regions were either drug susceptible or resistant only to streptomycin-spectinomycin encoded on a mobile genetic element and to nitrofurans. The report describes the arrival of a susceptible S. panama strain, its spread all over the country, and the evolution of progressively complex resistance patterns.
Chile↗
Molecular subtyping scheme for Salmonella panama.
We describe a genotyping scheme for Salmonella panama. Defined probes specific for the 16S rRNA gene and the DNA insertion element IS200 were generated by PCR from S. panama and were used to probe genomic Southern blots made with enzymes selected to cut within and outside the probed sequences. Plasmid profiles were determined. The typeability and discriminatory power of the individual methods were compared. Ribotyping with 16S rRNA gene probe alone was slightly more discriminatory than phage typing, but unlike the latter, ribotyping was able to type all strains. IS200 profiling was the single most discriminatory method for S. panama, having an index of discrimination (D) of 0.8 and 100% typeability. Plasmid profiling, which had moderate discriminatory power but only 50% typeability, was valuable as an adjunct technique. The use of all three methods together or simply the combination of IS200 profiling with the two most discriminatory enzymes and plasmid profiling yielded a molecular typing scheme whose discriminatory power (D = 0.97) approached the maximum theoretical value. This should prove both useful and robust for epidemiological investigations of S. panama.
Animals↗
[Phage-typing and tetracycline resistance in Salmonella panama strains of animal origin in the Federal Republic of Germany (1969-1975) (author's transl)].
505 out of 1369 S. panama strains isolated mainly from animals, foods, and feedstuffs from 1969 to 1975 were phage-typed. 41% (= 207) of the S. panama isolates examined originated from swine, 26% from cattle and calves, 15% from dogs, and 13% were from other animal species and materials. 465 strains (=92%) showed typical reactions. 23% were specified as phage-type A, 24% as phage-type B and 36% as phage-type G. Phage-types D, E, and F did not occur. In swine, being the most frequent carriers of S. panama, phage-types A, B, and G had nearly the same shares. In dogs, phage-type G predominated to which nearly one half of the examined S. panama isolates from this species belonged. 205 (=41%) out of 505 strains examined for their resistance to antibiotics proved to be tetracycline-resistant. All 123 strains of phage-type B were tetracycline-resistant, all 35 strains of phage-type C were tetracycline-sensitive. 5 strains of phage-type A exhibited transferable tetracycline-resistance determinants.
Animals↗
Kindler syndrome in native Americans from Panama: report of 26 cases.
OBJECTIVE: To investigate the clinical, genetic, and laboratory features of 26 patients with Kindler syndrome. DESIGN: Case series of patients recruited when they were seen at outpatient consultations in the Department of Dermatology at the Changuinola Hospital in Bocas del Toro, Panama, between May 1986 and December 1990. SETTING: Clinical history, physical examination, and laboratory studies were done at a community hospital in Panama. Twelve of the patients had further studies performed at a children's hospital in Costa Rica. PATIENTS: A total of 26 patients were entered into the study. They were members of the Ngöbe-Buglé tribe and resided in isolated villages in rural Panama. RESULTS: The major findings were skin fragility with blistering (100%), poikiloderma (96%), photosensitivity (92%), severe cutaneous atrophy (89%), hyperkeratosis of the palms and soles (81%), congenital acral blisters (81%), severe periodontal disease (81%), and phimosis (80% of male subjects). In 1 large family with 10 patients, inheritance of Kindler syndrome followed that of an autosomal recessive disease. Karyotypes in 3 patients and 1 unaffected father were normal. Findings from ultrastructural studies showed replication of lamina densa in 10 patients. CONCLUSIONS: To our knowledge, this study represents the largest series to date of patients with Kindler syndrome. The clinical features confirm previously reported cases, and segregation analysis confirms its autosomal recessive inheritance. We also report severe phimosis as a complication, which has not been previously described in this syndrome.
Adolescent↗
The Isthmus of Panama: a major physical barrier to gene flow in a highly mobile pantropical seabird.
To further test the hypothesis that the Isthmus of Panama is a major barrier to gene flow in pantropical seabirds, we applied phylogeographic methods to mitochondrial control sequence variation in masked booby (Sula dactylatra) populations on either side of the Isthmus of Panama and the southern tip of Africa. In accord with Steeves et al. (2003), we found that all Caribbean masked boobies with the 'secondary contact' cytochrome b haplotype (m-B) shared a control region haplotype (Sd_100), which grouped with Indian-Pacific haplotypes and not Caribbean-Atlantic haplotypes. In addition, Sd_100 was more closely related to control region haplotypes in the Indian Ocean than in the Pacific. We also found that the 'secondary contact' birds diverged more recently from extant populations in the Indian Ocean than in the Pacific. Thus, it appears that these masked boobies did not breach the Isthmus of Panama. Rather, birds likely dispersed around the southern tip of Africa during favourable oceanographic conditions in the Pleistocene.
Animals↗
Aging, acculturation, salt intake, and hypertension in the Kuna of Panama.
The indigenous Kuna who live on islands in the Panamanian Caribbean were among the first communities described with little age-related rise in blood pressure or hypertension. Our goals in this study were to ascertain whether isolated island-dwelling Kuna continue to show this pattern, whether migration to Panama City and its environs changed the patterns, and whether the island-dwelling Kuna have maintained their normal blood pressure levels despite partial acculturation, reflected in an increased salt intake. We enrolled 316 Kuna participants who ranged in age from 18 to 82 years. In 50, homogeneity was confirmed by documentation of an O+ blood group. In 92 island dwellers, diastolic hypertension was not identified and blood pressure levels were as low in volunteers over 60 years of age as in those between 20 and 30 years of age. In Panama City, conversely, hypertension prevalence was 10.7% and exceeded 45% in those over 60 years of age (P < .01), blood pressure levels were higher in the elderly, and there was a statistically significant positive relationship between age and blood pressure (P < .01). In Kuna Nega, a Panama City suburb designed to maintain a traditional Kuna lifestyle but with access to the city, all findings were intermediate. Sodium intake and excretion assessed in 50 island-dwelling Kuna averaged 135 +/- 15 mEq/g creatinine per 24 hours, exceeding substantially other communities free of hypertension and an age-related rise in blood pressure. Despite partial acculturation, the island-dwelling Kuna Indians are protected from hypertension and thus provide an attractive population for examining alternative mechanisms.
Acculturation↗
Overexposure of radiation therapy patients in Panama: problem recognition and follow-up measures.
This report summarizes and analyzes the responses of various organizations that provided assistance to the National Oncology Institute (Instituto Oncológico Nacional, ION) of Panama following the overexposure of 28 radiation therapy patients at the ION in late 2000 and early 2001. The report also looks at the long-term measures that were adopted at the ION in response to the overexposure incident, as well as implications that the incident has for other cancer treatment centers worldwide. In March 2001, the director of the ION was notified of serious overreactions in patients undergoing radiation therapy for cancer treatment. Of the 478 patients treated for pelvic cancers between August 2000 and March 2001, 3 of them had died, possibly from an overdose of radiation. In response, the Government of Panama invited international experts to carry out a full investigation of the situation. Medical physicists from the Pan American Health Organization (PAHO) were among those invited. They ascertained that 56 patients treated with partially blocked teletherapy fields for cancers of the uterine cervix, endometrium, prostate, or rectum, had had their treatment times calculated using a computerized treatment planning system. PAHO's medical physicists calculated the absorbed doses received by the patients and found that, of these 56 patients, only 11 had been treated with acceptable errors of +/-5%. The doses received by 28 of the 56 patients had errors ranging from +10 to +105%. These are the patients identified by ION physicists as overexposed. Twenty-three of the 28 overexposed patients had died by September 2005, with at least 18 of the deaths being from radiation effects, mostly rectal complications. The clinical, psychological, and legal consequences of the overexposures crippled cancer treatments in Panama and prompted PAHO to assess radiation oncology practices in the countries of Latin American and the Caribbean. ION clinicians evaluated the outcome of 125 non-overexposed patients who had been treated in the same time period and for the same cancer sites as the overexposed patients. The clinicians uncovered a larger recurrence of cervical cancers than expected. The finding prompted PAHO to launch an initiative for the accreditation of radiation oncology centers in Latin America and the Caribbean, working in collaboration with professional societies for radiation oncologists, medical physicists, and radiotherapy technologists. The Latin American Association for Radiation Oncology (Asociación Latinoamericana de Terapia Radiante Oncológica) has established an accreditation commission. Accreditation will require that centers implement a comprehensive radiation oncology quality assurance program that follows international guidelines. Statistical data on patient outcomes will be collected in order to document needs in radiotherapy centers in Latin America and the Caribbean and to define future strategies for cancer treatment.
Humans↗
First opportunities to try drugs and the transition to first drug use: evidence from a national school survey in Panama.
In recent evidence from the United States, there generally are no male-female differences in the probability of drug use among persons who report an opportunity to try the drugs. This is an important observation that might help us understand male-female differences in later drug use and dependence, but the observation needs to be replicated elsewhere. We begin this replication process using data from a 1996 national school survey of drug involvement among 6,477 students age 12-18 in Panama. We first examine the occurrence of an opportunity to use drugs by grade. We then follow these analyses with an examination of male-female differences in drug opportunity patterns. We found opportunities to use drugs and actual drug use to be greater at higher grade levels. Also, we found the probability of making a transition to use, given an opportunity, to be more likely among upper-grade students. Consistent with results observed in the United States, we found males in Panama to be more likely to have an opportunity to use marijuana, crack-cocaine, and other forms of cocaine, but not more likely than females to make a transition into drug use once an opportunity had occurred to try each drug. These findings are discussed in relation to the epidemiology and prevention of drug use in Panama and elsewhere, and future research on male-female differences in drug involvement.
Adolescent↗