RESUMEN
BACKGROUND: Before the SARS-CoV-2 Delta variant arrived in Vietnam, case rates suggested seroprevalence of SARS-CoV-2 was low. Beginning in March 2021, we assessed different dosing schedules and adverse events following immunization (AEFIs) for ChAdOx1 nCoV-19 vaccine among healthcare workers (HCWs). METHODS: We performed a prospective cohort study to estimate the prevalence of IgG antibodies to SARS-CoV-2 before and after ChAdOx1 nCoV-19 vaccination. We conducted antibody testing among HCWs in February 2021 (baseline), before the second dose (June-July 2021), and 1 and 3 months after the second dose. We detected antibodies to SARS-CoV-2 using Tetracore® FlexImmArray™, and surrogate neutralizing antibodies using GenScript cPass™. Neither assay can distinguish natural from vaccine-induced antibodies. We assessed AEFIs through interview post-dose 1 and 1 month post-dose 2. RESULTS: Before vaccination, 1/617 participants (0.16%) had antibodies to SARS-CoV-2. Of these 617, 405 were vaccinated with ChAdOx1 nCoV-19 with 4-8- (60%), 9-12- (27%), or ≥13-week (13%) intervals between the 2 doses. Three months following series completion, 99% and 97% of vaccinated participants had ≥1 sample with detectable antibodies and surrogate neutralizing antibodies against SARS-CoV-2, respectively. We observed no significant differences among those with different dosing intervals at last follow-up. All participants reported PCR testing for SARS-CoV-2 during the study; 2 (0.5%) were laboratory-confirmed. AEFIs were more frequent post-dose 1 (81%) vs post-dose 2 (21%). CONCLUSIONS: In this population, regardless of dosing interval, ChAdOx1 nCoV-19 induced antibodies within 3 months of the second dose. These findings may offer flexibility to policymakers when balancing programmatic considerations with vaccine effectiveness.
Asunto(s)
COVID-19 , Vacunas Virales , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Pueblo Asiatico , COVID-19/epidemiología , COVID-19/prevención & control , ChAdOx1 nCoV-19 , Personal de Salud , Humanos , Inmunoglobulina G , Estudios Prospectivos , SARS-CoV-2 , Estudios Seroepidemiológicos , Vacunación , Vietnam/epidemiologíaRESUMEN
BACKGROUND: Canine-mediated human rabies deaths typically occur in poor and rural populations with limited access to rabies biologics: vaccine and immunoglobulin. A critical aspect of reducing rabies deaths is understanding how these countries procure, deliver, and forecast rabies biologics. Vietnam is one of the few endemic countries where biologics is widely available. However, a formal evaluation of its current rabies biologics distribution system has not been conducted. METHODS: In 2017, we conducted a formal evaluation of Vietnam's rabies biologics distribution system. Our goals were (1) to identify centers providing rabies biologics (2) identify costs to the patient and centers and (3) assess the rabies biologic procurement and delivery system at eligible district and provincial centers (provides and orders biologics for itself and other centers directly from the manufacture). To conduct the formal evaluation, we developed a standardized survey that was distributed to centers. RESULTS: Of the 780 designated rabies biologics centers in Vietnam, 659 (84%) of them provide rabies immunoglobulin (eRIG), vaccine, or both. Of the 177 eligible centers, 90% (160) responded to the survey. The average costs to patients were $8.45 (range: 5.43-12.77) for one dose of IM injection, $13.90 (range: 11.86-16.71) for domestic eRIG, and $23 (21.11-27.11) for imported eRIG. Respondents reported experiencing delays in receiving vaccine in 50 centers and eRIG in 14 centers within the past year. Respondents stated their top three challenges in providing biologics were: delays or shortages from manufactures, lack of funds to pay for biologics, and the high cost of biologics. CONCLUSIONS AND RELEVANCE: Despite the wide availability of biologics in Vietnam, more work is needed to provide affordable and reliable supply of biologics to patients. This includes the expansion of ID injection use throughout the country to lower vaccine demand, and decrease the costs to centers and patients. Furthermore, a more coordinated effort to share biologics among centers, possibly through a more centralized system at the provincial level may alleviate delays and shortages.
Asunto(s)
Productos Biológicos/provisión & distribución , Profilaxis Posexposición/métodos , Profilaxis Posexposición/provisión & distribución , Rabia/prevención & control , Productos Biológicos/economía , Costos de la Atención en Salud/estadística & datos numéricos , Gastos en Salud/estadística & datos numéricos , Humanos , Profilaxis Posexposición/economía , VietnamRESUMEN
BACKGROUND: Surgical response of patients with symptomatic biliary colic but atypical findings of gallbladder polyps, hyper-dynamic gallbladder and otherwise negative biliary workup are underrepresented in the literature from community practice. METHODS: A clinical outcome study with a retrospective design compared the short term and long term symptomatic improvement reported by patients with pre-operatively diagnosed biliary dyskinesia to all other biliary colic patients with atypical pre-operative diagnoses. All patients underwent surgery at Meridian Surgery Center from the years 2010-2017.600 patients were reviewed for biliary dyskinesia, gallbladder polyps, hyper-dynamic gallbladder and negative workup. RESULTS: Short term and long term results were compiled from a total 182 patients. Short term response rates were assessed from 74 biliary dyskinesia, 40 hyperdynamic, 23 gallbladder polyps, and 45 negative workup patients. Long term responses were received from 19 biliary dyskinesia patients, 11 hyperdynamic patients, 9 polyp patients, and 7 negative workup patients. Long term improvement among biliary dyskinesia patients was 84%, and 83% among patients with atypical findings, representing a long term drop in symptoms. There is no significant difference between symptom recovery of patients with biliary dyskinesia and those with another atypical diagnosis: hyper-dynamic (82%), polyps (89%), negative workup (57%). CONCLUSION: These results allow us to conclude that there is a comparable biliary colic improvement between biliary dyskinesia, gallbladder polyps, hyper-dynamic gallbladder and negative workup patients after cholecystectomy in both short term and long term follow up.
Asunto(s)
Discinesia Biliar/cirugía , Enfermedades de las Vías Biliares/cirugía , Colecistectomía Laparoscópica , Cólico/cirugía , Adulto , Colecistitis/cirugía , Femenino , Enfermedades de la Vesícula Biliar/cirugía , Cálculos Biliares/cirugía , Humanos , Masculino , Pólipos/cirugía , Estudios Retrospectivos , Escala Visual AnalógicaRESUMEN
BACKGROUND: Adhering to post-exposure prophylaxis (PEP): wound treatment, vaccine, and rabies immunoglobulin (RIG) is a crucial step in preventing rabies mortality. When PEP is widely available, a lack of adherence to the recommended treatment guidelines can also lead to death. Our objective was to understand characteristics associated with adherence to the vaccine regimen and RIG in Vietnam. METHODS: We obtained individual-level data on PEP adherence from registries at 10 sites located in five provinces. From these registries, we extracted epidemiologic characteristics of patients including the timing of PEP initiation and completion. We used descriptive analyses and logistic regression to examine patient characteristics associated with initiation and completion of RIG and vaccine. Based on reported rabies mortality, the government defined provincial rabies burden as medium-burden (<5 and >2 deaths) and high-burden (≥5 deaths). RESULTS: During 2014-2016, 15,646 patients received PEP in our study. Among 14,296 vaccinated patients, only 41.4% (5847) completed their five-dose intramuscular (IM) injections and 81.6% (133) of patients completed their eight-dose intradermal (ID) injections. Approximately 26% of patients received RIG. Patient characteristics associated with vaccine completion were females (44%), <15â¯years of age (44%), category 1 exposure (68%, bite location on leg (46%), bite from bat (56%), bite from a healthy animal (45%), high-burden province (86%), and district preventive center (49%). Disparities were revealed among provinces, with high-burden provinces having highest (86%) and lowest (7%) vaccine completion rates. CONCLUSIONS AND RELEVANCE: Vietnam has made tremendous progress towards reducing the burden of rabies. However, despite the wide availability of PEP, we found relatively low rates of vaccine completion. Our findings suggest provider training and patient education is needed to ensure appropriate treatment is completed. Moreover, our data suggest changes to information reported through the national surveillance system for monitoring good clinical practice for rabies prevention and control.
Asunto(s)
Cumplimiento de la Medicación/estadística & datos numéricos , Profilaxis Posexposición/métodos , Profilaxis Posexposición/estadística & datos numéricos , Rabia/prevención & control , Costo de Enfermedad , Humanos , Factores Inmunológicos/administración & dosificación , Aceptación de la Atención de Salud/estadística & datos numéricos , Rabia/epidemiología , Rabia/mortalidad , Vacunas Antirrábicas/administración & dosificación , Análisis de Supervivencia , Vietnam/epidemiologíaRESUMEN
A new Fe-based metal-organic framework (MOF), termed Fe-TBAPy Fe2(OH)2(TBAPy)·4.4H2O, was solvothermally synthesized. Structural analysis revealed that Fe-TBAPy is built from [Fe(OH)(CO2)2]∞ rod-shaped SBUs (SBUs = secondary building units) and 1,3,6,8-tetrakis(p-benzoate)pyrene (TBAPy4-) linker to form the frz topological structure highlighted by 7 Å channels and 3.4 Å narrow pores sandwiching between the pyrene cores of TBAPy4-. Consequently, Fe-TBAPy was used as a recyclable heterogeneous catalyst for benzene hydroxylation. Remarkably, the catalysis reaction resulted in high phenol yield and selectivity of 64.5% and 92.9%, respectively, which are higher than that of the other Fe-based MOFs and comparable with those of the best-performing heterogeneous catalysts for benzene hydroxylation. This finding demonstrated the potential for the design of MOFs with enhancing catalysis activity for benzene hydroxylation.
RESUMEN
A Zr(IV)-based metal-organic framework (MOF), termed reo-MOF-1 [Zr6O8(H2O)8(SNDC)4], composed of 4-sulfonaphthalene-2,6-dicarboxylate (HSNDC2-) linkers and Zr6O8(H2O)8(CO2)8 clusters was synthesized by solvothermal synthesis. Structural analysis revealed that reo-MOF-1 adopts the reo topology highlighted with large cuboctahedral cages (23 Å). This structure is similar to that found in DUT-52 (fcu topology), however, reo-MOF-1 lacks the body-centered packing of the 12-connected Zr6O4(OH)4(CO2)12 clusters, which is attributed to the subtle, but crucial influence in the bulkiness of functional groups on the linkers. The control experiments, where the ratio of H3SNDC/naphthalene-2,6-dicarboxylate linkers was varied, also support our finding that the bulky functionalities play a key role for defect-controlled synthesis. The reo-MOF-1A framework was obtained by linker exchange to yield a chemically and thermally stable material despite its large pores. Remarkably, reo-MOF-1A exhibits permanent porosity (Brunauer-Emmett-Teller and Langmuir surface areas of 2104 and 2203 m2 g-1, respectively). Owing to these remarkable structural features, reo-MOF-1A significantly enhances the yield in Brønsted acid-catalyzed reactions.
RESUMEN
Human rabies deaths are preventable through prompt administration of postexposure prophylaxis (PEP) with rabies immune globulin and rabies vaccine after exposure to a rabid animal (1); there are no known contraindications to receiving PEP (1,2). Despite widespread availability of PEP in Vietnam, in 2015 the Ministry of Health (MoH) received reports of pregnant and breastfeeding women with clinically diagnosed rabies. MoH investigated factors associated with these rabies cases. MoH found that, during 2015-2016, among 169 cases reported in Vietnam, two probable cases of rabies were reported in breastfeeding mothers and four in pregnant women, all of whom had been bitten by dogs. All six patients died. Three of the four pregnant women had cesarean deliveries. One of the three newborns died from complications believed to be unrelated to rabies; the fourth pregnant woman contracted rabies too early in pregnancy for the fetus to be viable. Two of the patients sought care from a medical provider or traditional healer; however, none sought PEP after being bitten. In each case, families reported the patient's fear of risk to the fetus or breastfed child as the primary barrier to receiving PEP. These findings highlight the need for public health messaging about the safety and effectiveness of PEP in preventing rabies among all persons with exposures, including pregnant and breastfeeding women.
Asunto(s)
Profilaxis Posexposición/estadística & datos numéricos , Vacunas Antirrábicas/administración & dosificación , Rabia/mortalidad , Vacunación/psicología , Adulto , Animales , Mordeduras y Picaduras , Lactancia Materna/estadística & datos numéricos , Perros , Femenino , Humanos , Embarazo , Mujeres Embarazadas/psicología , Rabia/prevención & control , Vietnam/epidemiologíaRESUMEN
The iron-organic framework VNU-20 was utilized as an active heterogeneous catalyst for the cross-dehydrogenative coupling of coumarins with Csp3-H bonds in alkylbenzenes, cyclohexanes, ethers, and formamides. The combination of DTBP as the oxidant and DABCO as the additive led to high yields of coumarin derivatives. The VNU-20 was more active towards this reaction than numerous other homogeneous and heterogeneous catalysts. Heterogeneous catalysis was confirmed for the cross-dehydrogenative coupling transformation utilizing the VNU-20 catalyst, and the contribution of active iron species in the liquid phase was insignificant. The iron-based framework was reutilized many times for the functionalization of coumarins without a remarkable decline in catalytic efficiency. To the best of our knowledge, these reactions of coumarins have not previously been conducted using heterogeneous catalysts.
RESUMEN
This article contains the datasets related to the research article "The long and short of commodity tails and their relationship to Asian equity markets"(Powell et al., 2017) [1]. The datasets contain the daily prices (and price movements) of 24 different commodities decomposed from the S&P GSCI index and the daily prices (and price movements) of three share market indices including World, Asia, and South East Asia for the period 2004-2015. Then, the dataset is divided into annual periods, showing the worst 5% of price movements for each year. The datasets are convenient to examine the tail risk of different commodities as measured by Conditional Value at Risk (CVaR) as well as their changes over periods. The datasets can also be used to investigate the association between commodity markets and share markets.
RESUMEN
A zirconium-based metal-organic framework, an effective heterogeneous catalyst, has been developed for the Friedel-Crafts benzoylation of aromatic compounds under microwave irradiation. Constructed by a Zr(iv) cluster and a linker 1,4-bis(2-[4-carboxyphenyl]ethynyl)benzene (H2CPEB), the MOF, possessing large pores and high chemical stability, was appropriate for the enhancement of Lewis acid activity under microwave irradiation. The reaction studies demonstrated that the material could give high yields for a few minutes and maintain its reactivity and structure over several cycles.
RESUMEN
New Zr(IV)- and Hf(IV)-based metal-organic framework photocatalysts, termed VNU-1 and VNU-2 (where VNU = Vietnam National University), were synthesized and their resulting structures fully characterized. By employing a highly π-conjugated linker, namely 1,4-bis(2-[4-carboxyphenyl]ethynyl)benzene, the optical absorption properties were effectively red-shifted into the visible light region. This strategy, coupled with the high water stability of the materials, led to enhanced MOF-driven photocatalytic degradation, under ultraviolet-visible light, of organic dye pollutants commonly found in wastewater.
RESUMEN
Situs inversus with dextrocardia is rare congenital anomaly. Coronary artery disease in such patients is quite rare. We reported a 52-year-old man with dextrocardia and chronic total occlusion at the proximal right coronary artery just after conus branch and severe stenosis at the proximal left anterior descending artery. He underwent successful percutaneous coronary intervention with stenting of total occluded right coronary artery and simultaneously stenting of the proximal left anterior descending artery.
Asunto(s)
Oclusión Coronaria/cirugía , Dextrocardia/complicaciones , Intervención Coronaria Percutánea , Enfermedad Crónica , Angiografía Coronaria , Oclusión Coronaria/complicaciones , Oclusión Coronaria/diagnóstico , Dextrocardia/diagnóstico , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Radiografía TorácicaRESUMEN
BACKGROUND: Coronary artery fistula (CAF) is a rare anomaly. Transcatheter CAF closure has been introduced using various materials, but only few data are available on the Guglielmi detachable coil (GDC). The advantage of using GDC for transcatheter CAF closure is more controllable, therefore much safer when compared to other coils. This report is about our experience in transcatheter closure of CAF using fibered GDC in our hospital. METHODS #ENTITYSTARTX00026; RESULTS: From 2002 to 2007, there were 10 patients with CAFs (age range: 28 to 56 year-old, 7 males) who underwent transcatheter CAF closure. There were a total of 19 CAFs which originated from right coronary (n = 5), left circumflex (n = 3), left anterior descending artery (n = 10) and left main trunk (n = 1). Median number of coil deployment for each fistula was 3 (range: 1 to 6). The pulmonary artery was the most common site of the distal communication of CAFs (n = 14), followed by right atrium (n = 3), left atrium (n = 1) and left ventricle (n = 1). Immediate coronary angiography after GDC deployment revealed no residual shunt in 12 (63.2%) CAFs, significant reduction of the flow in 5 (26.3%), while 2 (10.5%) could not be closed due to small size. Nine (90%) patients underwent a repeated angiography within 3 to 8 months. Among 12 CAFs that were occluded immediately post-deployment, there were 2 CAFs with insignificant residual flow. Among 6 CAFs with significantly decreased flow immediately post-deployment, 2 were occluded totally in the follow-up angiography. In total, 12 (70.5%) CAFs were occluded completely and 5 (29.5%) CAFs still had insignificant residual flow, which did not need any additional coil deployment. During a mean follow up of 4.3 ± 0.7 year, all patients remained symptom and complication free. CONCLUSIONS: The fibered GDC is a safe and effective method for percutaneous closure of the CAFs.
RESUMEN
The human immunodeficiency virus type 1 (HIV-1) genome encodes 18 proteins and 2 peptides. Four of these proteins encode high-affinity calmodulin-binding sites for which direct interactions with calmodulin have already been described. In this study, the HIV-1 proteome is queried using an algorithm that predicts calmodulin-binding sites revealing seven new putative calmodulin-binding sites including residues 34-56 of the transactivator of transcription (Tat). Tat is a 101-residue intrinsically disordered RNA-binding protein that plays a central role in the regulation of HIV-1 replication. Interactions between a Tat peptide (residues 34-56), melittin, a well-characterized calmodulin-binding peptide, and calmodulin were examined by direct binding studies, mass spectrometry, and fluorescence. The Tat peptide binds to both calcium-saturated and apo-calmodulin with a low micromolar affinity. Conformational changes induced in the Tat peptide were determined by circular dichroism, and residues in calmodulin that interact with the peptide were identified by HSQC NMR spectroscopy. Multiple interactions between HIV-1 proteins and calmodulin, a highly promiscuous signal transduction hub protein, may be an important mechanism by which the virus controls cell physiology.
Asunto(s)
Calmodulina/metabolismo , Proteínas del Virus de la Inmunodeficiencia Humana/metabolismo , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/metabolismo , Secuencia de Aminoácidos , Calmodulina/química , Dicroismo Circular , Biología Computacional , Proteínas del Virus de la Inmunodeficiencia Humana/química , Humanos , Espectrometría de Masas , Meliteno , Modelos Moleculares , Datos de Secuencia Molecular , Resonancia Magnética Nuclear Biomolecular , Unión Proteica , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/químicaRESUMEN
The HIV-1 transactivator of transcription (Tat) is a protein essential for virus replication. Tat is an intrinsically disordered RNA-binding protein that, in cooperation with host cell factors cyclin T1 and cyclin-dependent kinase 9, regulates transcription at the level of elongation. Tat also interacts with numerous other intracellular and extracellular proteins, and is implicated in a number of pathogenic processes. The physico-chemical properties of Tat make it a particularly challenging target for structural studies: Tat contains seven Cys residues, six of which are essential for transactivation, and is highly susceptible to oxidative cross-linking and aggregation. In addition, a basic segment (residues 48-57) gives the protein a high net positive charge of +12 at pH 7, endowing it with a high affinity for anionic polymers and surfaces. In order to study the structure of Tat, both alone and in complex with partner molecules, we have developed a system for the bacterial expression and purification of 6xHistidine-tagged and isotopically enriched (in N15 and C13) recombinant HIV-1 Tat(1-72) (BH10 isolate) that yields large amounts of protein. These preparations have facilitated the assignment of 95% of the backbone NMR resonances. Analysis by mass spectrometry and NMR demonstrate that the cysteine-rich Tat protein is unambiguously reduced, monomeric, and unfolded in aqueous solution at pH 4.
Asunto(s)
VIH-1/química , VIH-1/genética , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/química , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/aislamiento & purificación , Humanos , Espectrometría de Masas , Resonancia Magnética Nuclear Biomolecular , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genéticaRESUMEN
All the possible uranium(VI, V, IV) oxides, fluorides and oxofluorides were studied theoretically by using density functional theory (DFT) in the generalised gradient approximation (GGA), and three different relativistic methods (all-electron scalar four component Dyall RESC method (AE), relativistic small-core ECPs, and zeroth order regular approximation ZORA). In order to test different correlation methods, for the two former relativistic methods hybrid DFT, and, for the AE method, MP2 molecular orbital calculations were performed as well. Single-point AE-CCSD(T) energies were calculated on MP2 geometries as well. Energies of the uranium(VI) and (V) oxofluorides dissociation, uranium(VI) fluoride hydrolysis and oxofluoride disproportionation were calculated and compared against the available experimental thermochemical data. AE-CCSD(T) energies were the closest to the experiment. For GGA DFT methods, all the relativistic methods used yield similar results. For thermochemistry, the best quantitative agreement with the experimental and CCSD(T) values for both U=O and U-F bond strengths was obtained with hybrid DFT methods, provided that a reliable basis set was used. Both the GGA DFT and MP2 MO methods show overbinding of these bonds; moreover, this overbinding was found to be not uniform but strongly dependent on the coordination environment of the uranium atom in each case. U=O vibrational frequencies given by hybrid DFT, however, are systematically overestimated, and are better reproduced by GGA DFT; MP2 values usually fall in-between. Reaction enthalpies, U=O frequencies and complex geometries given by the PBE, MPBE, BPBE, BLYP and OLYP GGA functionals are quite similar, with OLYP performing slightly better than the others but still not as good as hybrid DFT. The geometries of the molecules are found to be influenced by the following factors: the inverse transinfluence (ITI) of the oxygen ligand and, for U(V), and U(IV), the Jahn-Teller distortion.
RESUMEN
This study uses data from two surveys performed in 1991 and 1994 in a mountainous district of northern Vietnam. The aim was to describe the utilization of family planning, antenatal care, delivery and immunization services during a period of rapid structural change in the health services in general and implementation of a primary health care project in the study area. This project was aimed at increasing access to health services and improving the quality of primary health care services. Factors influencing the utilization of reproductive health services were analyzed. The contraceptive prevalence among women aged 15-49 increased significantly from 48% in 1991 to 60% in 1994. The most commonly used contraceptive method was intra-uterine devices. The BCG coverage among children under five years of age increased from 36 to 70%. The proportion of pregnant women receiving three antenatal check-ups, as recommended by the health authorities was low and increased slightly from 15% in 1991 to 20% in 1994. About one third of the pregnant women were delivered in health care institutions during this period. The utilization of family planning, antenatal care and delivery services varied with ethnicity and was positively related to the mother's educational level both in 1991 and 1994. There is a need to strengthen the reproductive health services, especially antenatal care and delivery services, in terms of improving the quality of care and accessibility to women. Efforts should be made to reach women with a low education level as well as those belonging to ethnic minorities.
Asunto(s)
Servicios de Planificación Familiar/estadística & datos numéricos , Inmunización/estadística & datos numéricos , Servicios de Salud Materna/estadística & datos numéricos , Atención Primaria de Salud/estadística & datos numéricos , Adolescente , Adulto , Femenino , Reforma de la Atención de Salud , Conocimientos, Actitudes y Práctica en Salud , Investigación sobre Servicios de Salud , Humanos , Persona de Mediana Edad , Madres/educación , Innovación Organizacional , Embarazo , Encuestas y Cuestionarios , VietnamRESUMEN
Dihaploid genotypes of potato, containing the dominant allele for extreme resistance to PVX and/or PVY, were used in a fusion program in order to analyze the behaviour of the two monogenetic resistances after fusion. Eighteen different fusion combinations were performed and regenerated hybrids were tested by ELISA for their virus resistance. In most of the combinations an addition of the two qualities was found, but a few deviating clones were observed. The possible reasons for the phenotypic disappearance of resistant alleles are discussed.