The roles of stakeholder experience and organizational learning in declining mass drug administration coverage for lymphatic filariasis in Port-au-Prince, Haiti: A case study.

The World Health Organization (WHO) defines an effective round of mass drug administration (MDA) for lymphatic filariasis (LF) as one that reaches at least 65% of the target population. In its first round of MDA in 2011-2012, the National Program to Eliminate LF in Haiti achieved a 79% epidemiological coverage in urban Port-au-Prince. In 2013, coverage dropped below the WHO threshold and has declined year-over-year to a low of 41% in 2017. We conducted a retrospective qualitative case study to identify key factors behind the decline in coverage in Port-au-Prince and ways to address them. Our findings suggest that the main contributors to the decline in MDA coverage appear to be the absence of effective documentation of practices, reporting, analysis, and program quality improvement-i.e., learning mechanisms-within the program's MDA design and implementation strategy. In addition to their contribution to the program's failure to meet its coverage targets, these deficits have resulted in a high cost for the MDA campaign in both lost momentum and depleted morale. Through a proposed operating logic model, we explore how the pathway from program inputs to outcomes is influenced by a wide array of mediating factors, which shape potential participants' experience of MDA and, in turn, influence their reasoning and decisions to take, or not take, the pills. Our model suggests that the decisions and behavior of individuals are a reflection of their overall experience of the program itself, mediated through a host of contextual factors, and not simply the expression of a fixed choice or preference. This holistic approach offers a novel and potentially valuable framing for the planning and evaluation of MDA strategies for LF and other diseases, and may be applicable in a variety of global health programs.

Immunomodulation Properties of Solid-State Fermented Laetiporussulphureus Ethanol Extracts in Chicken Peripheral Blood Monocytes In Vitro

Laetiporus sp. is recognized as a fungal species traditionally used for medicinal purposes. This study investigated the in-vitro effects of solid-state fermented Laetiporussulphureus ethanol extracts (LSE) for their immunomodulatory potential. Bioactive levels detected in the LSE on different days throughout the fermentation period revealed that the 12th day was the most efficient, with 7.19 ± 0.66 GAE/g DM crude phenolic content, 2.71 ± 0.03 UAE/g DM crude triterpenoid content, 12.93 ± 0.88 GCE/g DM crude polysaccharides, and 96.44 ± 0.2 mg/g DM ergosterol content. In-vitroLSE tests on chPBMC showed no cytotoxicity within a range of 0.05-1 mg/mL, but LPS-inhibited cell viability was improved, as well as LPS-induced nitric oxide (NO) production and mRNA levels of nuclear factor kappa B (NFB), Toll-like receptor 4 (TLR4), inducible nitric oxide synthase (iNOS), and interleukin (IL)-1were attenuated Furthermore, the direct application of LSE on chPBMC showed a small but not significant increase in NFB, TLR4, and iNOS mRNA expression compared with the control group. These results indicate the potential of LSE to modulate LPS-triggered inflammation processes involving TLR4 and NFB mediation. However, further experiments are required to determine the specific pathway.(AU)

Immunomodulation Properties of Solid-State Fermented Laetiporussulphureus Ethanol Extracts in Chicken Peripheral Blood Monocytes In Vitro

Laetiporus sp. is recognized as a fungal species traditionally used for medicinal purposes. This study investigated the in-vitro effects of solid-state fermented Laetiporussulphureus ethanol extracts (LSE) for their immunomodulatory potential. Bioactive levels detected in the LSE on different days throughout the fermentation period revealed that the 12th day was the most efficient, with 7.19 ± 0.66 GAE/g DM crude phenolic content, 2.71 ± 0.03 UAE/g DM crude triterpenoid content, 12.93 ± 0.88 GCE/g DM crude polysaccharides, and 96.44 ± 0.2 mg/g DM ergosterol content. In-vitroLSE tests on chPBMC showed no cytotoxicity within a range of 0.05-1 mg/mL, but LPS-inhibited cell viability was improved, as well as LPS-induced nitric oxide (NO) production and mRNA levels of nuclear factor kappa B (NFB), Toll-like receptor 4 (TLR4), inducible nitric oxide synthase (iNOS), and interleukin (IL)-1were attenuated Furthermore, the direct application of LSE on chPBMC showed a small but not significant increase in NFB, TLR4, and iNOS mRNA expression compared with the control group. These results indicate the potential of LSE to modulate LPS-triggered inflammation processes involving TLR4 and NFB mediation. However, further experiments are required to determine the specific pathway.

First record of the root knot nematode, Meloidogyne minor in New Zealand with description, sequencing information and key to known species of Meloidogyne in New Zealand.

Meloidogyne minor Karssen et al. 2004 was collected from perennial ryegrass (Lolium perenne L.) growing in a sports ground in Christchurch, New Zealand. This is a new record for M. minor, the first report of this nematode occurring in New Zealand, and the second report from the southern hemisphere (after Chile). In general, the New Zealand isolate of M. minor corresponds well to the descriptions of M. minor given by Karssen et al. (2004). The New Zealand isolate is characterized by having a female with dorsally curved stylet, 13-14 µm long, with transversely ovoid knobs slightly sloping backwards from shaft; rounded perineal pattern; and male with stylet 16-19 µm long, large transversely ovoid knobs sloping slightly backwards from shaft; head region not set off, labial disc elevated, lateral lips prominent; and second stage juvenile 370-390 µm long, with hemizonid posterior but adjacent to excretory pore; tail 53-63 µm long; and a distinct hyaline tail terminus 14-18 µm long. In addition, molecular phylogeny using near full length small subunit (SSU), D2/D3 expansion segments of the large subunit (LSU), the internal transcribed spacer region (ITS1 and 2), and the intergenic spacer (IGS2) of the ribosomal rDNA supports the identification.

Analysis of α1 and α2 globin genes among patients with hemoglobin Adana in Malaysia.

Hemoglobin (Hb) Adana [HBA2: c179G>A (or HBA1); p.Gly60Asp] is a non-deletional α-thalassemia variant found in Malaysia. An improvement in the molecular techniques in recent years has made identification of Hb Adana much easier. For this study, a total of 26 Hb Adana α-thalassemia intermedia and 10 Hb Adana trait blood samples were collected from patients. Common deletional and non-deletional α-thalassemia genotypes were determined using multiplex gap polymerase chain reaction (PCR) and multiplex ARMS PCR techniques. Identification of the Hb Adana location on the α-globin gene was carried out using genomic sequencing and the location of the mutation was confirmed via restriction fragment length polymorphism-PCR. Among the 36 samples, 24 (66.7%) had the -α(3.7)/α(Cd59)α mutation, while the -α(3.7)/α(Cd59)α mutation accounted for 2 samples (5.6%) and the remaining 10 (27.8%) samples were α/α(Cd59)α. All 36 samples were found to have the Hb Adana mutation on the α2-globin gene. The position of the α-globin gene mutation found in our cases was similar to that reported in Indonesia (16%) but not to that in Turkey (0.6%). Our results showed that the Hb Adana mutation was preferentially present in the α2-globin genes in Malays compared to the other ethnicities in Malaysia. Thus, the Malays might have similar ancestry based on the similarities in the Hb Adana position.

The impact of Advanced Life Support in Obstetrics (ALSO) training in low-resource countries.

OBJECTIVE: To examine the effects of the Advanced Life Support in Obstetrics (ALSO) program on maternal outcomes in four low-income countries. METHODS: Data were obtained from single-center, longitudinal cohort studies in Colombia, Guatemala, and Honduras, and from an uncontrolled prospective trial in Tanzania. RESULTS: In Colombia, maternal morbidity and the number of near misses increased after ALSO training, but maternal mortality decreased. In Guatemala, sustained reductions in overall maternal mortality and mortality from postpartum hemorrhage (PPH) were recorded after ALSO implementation. In Honduras, there was a significant decrease in episiotomy rates, and increases in active management of the third stage of labor (AMTSL), vacuum-assisted delivery, and reported comfort managing obstetric emergencies. In Tanzania, the frequency of PPH and severe PPH decreased after training, while management improved. CONCLUSION: In low-income countries, ALSO training was associated with decreased in-hospital maternal mortality, episiotomy use, and PPH. AMTSL and vacuum-assisted vaginal delivery increased in frequency after ALSO training.

Detection of Trypanosoma cruzi DNA in blood by PCR is associated with Chagas cardiomyopathy and disease severity.

BACKGROUND: The significance of detection of Trypanosoma cruzi DNA in blood of antibody-positive patients for risk of development of Chagas heart disease is not well established. The objective of this study was to compare detection of T. cruzi DNA with known clinical and laboratory markers of Chagas cardiomyopathy (CC) severity. METHODS: This is a case-control study nested within a retrospective cohort developed in Brazil to understand the natural history of Chagas disease. The study enrolled 499 T. cruzi seropositive blood donors (SP-BD) and 488 frequency matched seronegative control donors (SN-BD) who had donated between 1996 and 2002, and 101 patients with clinically diagnosed CC. In 2008-2010 all enrolled subjects underwent a health questionnaire, medical examination, electrocardiograms and echocardiograms and polymerase chain reaction (PCR) analyses. A blinded panel of three cardiologists adjudicated the outcome of CC. Trypanosoma cruzi kinetoplast minicircle sequences were amplified by real-time PCR using an assay with a sensitivity of one parasite per 20 mL of blood. All testing was performed on coded samples. RESULTS: Rates of PCR detection of T. cruzi DNA were significantly (P = 0.003) higher in CC patients and SP-BD diagnosed with CC (79/105 [75.2 %]) compared with SP-BD without CC (143/279 [51.3%]). The presence of parasitaemia was significantly associated with known markers of disease progression such as QRS and QT interval duration, lower left ventricular ejection fraction, higher left ventricular index mass, and elevated troponin and NTpro-BNP levels. CONCLUSION: Trypanosoma cruzi PCR positivity is associated with presence and severity of cardiomyopathy, suggesting a direct role of parasite persistence in disease pathogenesis.

Genetic relationships in an international collection of Puccinia horiana isolates based on newly identified molecular markers and demonstration of recombination.

The obligate biotrophic pathogen Puccinia horiana is the causal agent of chrysanthemum white rust. Although P. horiana is a quarantine organism, it has been able to spread to most chrysanthemum-producing regions in the world since the 1960s; however, the transfer routes are largely obscure. An extremely low level of allelic diversity was observed in a geographically diverse set of eight isolates using complexity reduction of polymorphic sequences (CRoPS) technology. Only 184 of the 16,196 contigs (1.1%) showed one or more single-nucleotide polymorphisms (SNPs). Thirty-two SNPs and one simple-sequence repeat were translated into molecular markers and used to genotype 45 isolates originating from North and South America, Asia, and Europe. In most cases, phylogenetic clustering was related to geographic origin, indicating local establishment. The European isolates mostly grouped in two major populations that may relate to the two historic introductions previously reported. However, evidence of recent geographic transfer was also observed, including transfer events between Europe and South America and between Southeast Asia and Europe. In contrast with the presumed clonal propagation of this microcyclic rust, strong indications of marker recombination were observed, presumably as a result of anastomosis, karyogamy, and somatic meiosis. Recombination and transfer also explain the geographic dispersal of specific markers. A near-to-significant correlation between the genotypic data and previously obtained pathotype data was observed and one marker was associated with the most virulent pathotype group. In combination with a fast SNP detection method, the markers presented here will be helpful tools to further elucidate the transfer pathways and local survival of this pathogen.

Recombinant expression and biochemical characterization of sugarcane legumain.

Plant legumains, also termed vacuolar processing enzymes (VPEs), are cysteine peptidases that play key roles in plant development, senescence, programmed cell death and defense against pathogens. Despite the increasing number of reports on plant cysteine peptidases, including VPEs, the characterization of sugarcane VPEs and their inhibition by endogenous cystatins have not yet been described. This is the first report of the biochemical characterization of a sugarcane cysteine peptidase. In this work, a recombinant sugarcane legumain was expressed in Pichia pastoris and characterized. Kinetic studies of the recombinant CaneLEG revealed that this enzyme has the main characteristics of VPEs, such as self-activation and activity under acidic pH. CaneLEG activity was strongly inhibited when incubated with sugarcane cystatin 3 (CaneCPI-3). Quantitative analysis of CaneLEG and CaneCPI-3 gene expression indicated a tissue-specific expression pattern for both genes throughout sugarcane growth, with the strong accumulation of CaneLEG transcripts throughout the internode development. Furthermore, the CaneLEG and CaneCPI-3 genes exhibited up-regulation in plantlets treated with abscisic acid (ABA). These results suggest that CaneCPI-3 may be a potential endogenous inhibitor of CaneLEG and these genes may be involved in plant stress response mediated by ABA. Also, the expression analysis provides clues for the putative involvement of CaneLEG and CaneCPI-3 in sugarcane development and phytohormone response.

Development of microsatellite primers for Jatropha curcas (Euphorbiaceae) and transferability to congeners.

PREMISE OF THE STUDY: Microsatellite primers were developed for Jatropha curcas (Euphorbiaceae), a tree species with large potential for biofuel production, to investigate its natural genetic diversity and mating system to facilitate the establishment of tree improvement and conservation programs. METHODS AND RESULTS: Using a protocol for genomic library enrichment, 104 clones containing 195 repeat motifs were identified. Primer pairs were developed for 40 microsatellite loci and validated in 41 accessions of J. curcas from six provenances. Nine loci were polymorphic revealing from two to eight alleles per locus, and six primers were able to amplify alleles in the congeners J. podagrica, J. pohliana, and J. gossypifolia, but not in other Euphorbiaceae species, such as Hevea brasiliensis, Manihot esculenta, or Ricinus communis. CONCLUSIONS: The primers developed here revealed polymorphic loci that are suitable for genetic diversity and structure, mating system, and gene flow studies in J. curcas, and some congeners.

Variable number of tandem repeat markers in the genome sequence of Mycosphaerella fijiensis, the causal agent of black leaf streak disease of banana (Musa spp).

We searched the genome of Mycosphaerella fijiensis for molecular markers that would allow population genetics analysis of this plant pathogen. M. fijiensis, the causal agent of banana leaf streak disease, also known as black Sigatoka, is the most devastating pathogen attacking bananas (Musa spp). Recently, the entire genome sequence of M. fijiensis became available. We screened this database for VNTR markers. Forty-two primer pairs were selected for validation, based on repeat type and length and the number of repeat units. Five VNTR markers showing multiple alleles were validated with a reference set of isolates from different parts of the world and a population from a banana plantation in Costa Rica. Polymorphism information content values varied from 0.6414 to 0.7544 for the reference set and from 0.0400 and 0.7373 for the population set. Eighty percent of the polymorphism information content values were above 0.60, indicating that the markers are highly informative. These markers allowed robust scoring of agarose gels and proved to be useful for variability and population genetics studies. In conclusion, the strategy we developed to identify and validate VNTR markers is an efficient means to incorporate markers that can be used for fungicide resistance management and to develop breeding strategies to control banana black leaf streak disease. This is the first report of VNTR-minisatellites from the M. fijiensis genome sequence.

Red tides in the Gulf of Mexico: Where, when, and why?

[1] Independent data from the Gulf of Mexico are used to develop and test the hypothesis that the same sequence of physical and ecological events each year allows the toxic dinoflagellate Karenia brevis to become dominant. A phosphorus-rich nutrient supply initiates phytoplankton succession, once deposition events of Saharan iron-rich dust allow Trichodesmium blooms to utilize ubiquitous dissolved nitrogen gas within otherwise nitrogen-poor sea water. They and the co-occurring K. brevis are positioned within the bottom Ekman layers, as a consequence of their similar diel vertical migration patterns on the middle shelf. Upon onshore upwelling of these near-bottom seed populations to CDOM-rich surface waters of coastal regions, light-inhibition of the small red tide of ~1 ug chl l(-1) of ichthytoxic K. brevis is alleviated. Thence, dead fish serve as a supplementary nutrient source, yielding large, self-shaded red tides of ~10 ug chl l(-1). The source of phosphorus is mainly of fossil origin off west Florida, where past nutrient additions from the eutrophied Lake Okeechobee had minimal impact. In contrast, the P-sources are of mainly anthropogenic origin off Texas, since both the nutrient loadings of Mississippi River and the spatial extent of the downstream red tides have increased over the last 100 years. During the past century and particularly within the last decade, previously cryptic Karenia spp. have caused toxic red tides in similar coastal habitats of other western boundary currents off Japan, China, New Zealand, Australia, and South Africa, downstream of the Gobi, Simpson, Great Western, and Kalahari Deserts, in a global response to both desertification and eutrophication.

A randomized controlled trial of genotypic HIV drug resistance testing in HIV-1-infected children: the PERA (PENTA 8) trial.

OBJECTIVE: To evaluate the longer-term utility of genotypic resistance testing in HIV-1-infected children with virological failure. METHODS: Children aged 3 months-18 years switching antiretroviral therapy (ART) with HIV-1 RNA > 2,000 copies/ml were randomized between genotypic testing (Virtual Phenotype) and no testing at baseline and subsequent virological failures. Children were followed to at least 96 weeks. RESULTS: One hundred and seventy eligible children, from 24 clinical centres in six countries, were randomized to resistance testing (n = 87) or no testing (n = 83) between June 2000-July 2003. At baseline, mean HIV-1 RNA and CD4+ T-cell percentage were 4.7 log10 copies/ml and 20%, respectively. Children had taken ART for a mean of 5 years; 24% had received all three classes, 53% nucleoside reverse transcriptase inhibitors (NRTIs)+protease inhibitors (PIs), 9% NRTIs+non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 14% NRTIs only. There was no difference between the arms in the drug classes or the individual PIs/NNRTIs prescribed. However, 49% in the resistance test arm (RT) versus 19% in the no-test arm (NT) continued at least one NRTI from their failing regimen; 56% versus 19% were prescribed didanosine+stavudine as their NRTI backbone. Adjusting for baseline HIV-1 RNA, mean reductions in HIV-1 RNA at 48 weeks were 1.51 log10 copies/ml in the RT arm and 1.23 in the NT arm (P = 0.3); the difference between the arms was smaller at week 96 (RT: 1.50, NT: 1.47; P = 0.9). CONCLUSION: In this first paediatric trial of resistance testing, we observed a substantial difference in NRTI-prescribing behaviour across arms. However statistically significant evidence of a long-term virological or immunological benefit was not observed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN14367816.

Family medicine in Cuba: community-oriented primary care and complementary and alternative medicine.

Family physicians in Cuba and the United States operate within very different health systems. Cuba's health system is notable for achieving developed country health outcomes despite a developing country economy. The authors of this study traveled to Cuba and reviewed the literature to investigate which practices of Cuban family physicians might be applicable for US family physicians wishing to learn from the Cuban experience. We found that community-oriented primary care (COPC) and complementary and alternative medicine (CAM) are well developed within the Cuban medical system. Because COPC and CAM are already recommended by US family medicine professional bodies, US family physicians may want to learn from the Cuban experience and perhaps incorporate elements into their individual practices.

Advanced life support in obstetrics in Ecuador: teaching the teachers.

The advanced life support in obstetrics (ALSO) course is designed to help maternity care providers prepare for obstetrical emergencies. A team of 12 US physicians and a medical interpreter recently taught the ALSO course in Ecuador, with the goal of addressing Ecuador's high maternal and infant mortality rates. To have a greater impact, a teach-the-teacher model was used so that Ecuadorian physicians can now hold their own ALSO courses. In the process of implementing the courses, valuable lessons were learned which can be applied to future ALSO courses in developing countries and in the United States.

Following adsorption kinetics at electrolyte/metal interfaces through crystal truncation scattering: sulfur on Au(111).

Combining electrochemical methods, in situ scanning tunneling microscopy, and surface x-ray diffraction allowed study of the structure and kinetics of S/Au(111) electrodes in aqueous electrolytes under potential control. Integrated intensities of a particular crystal truncation rod at anti-Bragg conditions were used to trace the sulfur adsorption and desorption as a function of electrode potential in real time. The S desorption is a first order process and the adsorption follows a Langmuir isotherm. A weakly bound S layer is found on the surface before charge transfer, and then specific adsorption occurs.

Impact of age on perioperative complications and length of stay in patients undergoing noncardiac surgery.

BACKGROUND: Major surgical procedures are performed with increasing frequency in elderly persons, but the impact of age on resource use and outcomes is uncertain. OBJECTIVE: To evaluate the influence of age on perioperative cardiac and noncardiac complications and length of stay in patients undergoing noncardiac surgery. DESIGN: Prospective cohort study. SETTING: Urban academic medical center. PATIENTS: Consecutive sample of 4315 patients 50 years of age or older who underwent nonemergent major noncardiac procedures. MEASUREMENTS: Major perioperative complications (cardiac and noncardiac), in-hospital mortality, and length of stay. RESULTS: Major perioperative complications occurred in 4.3% (44 of 1015) of patients 59 years of age or younger, 5.7% (93 of 1646) of patients 60 to 69 years of age, 9.6% (129 of 1341) of patients 70 to 79 years of age, and 12.5% (39 of 313) of patients 80 years of age or older (P < 0.001). In-hospital mortality was significantly higher in patients 80 years of age or older than in those younger than 80 years of age (0.7% vs. 2.6%, respectively). Multivariate analyses indicated an increased odds ratio for perioperative complications or in-hospital mortality in patients 70 to 79 years of age (1.8 [95% CI, 1.2 to 2.7]) and those 80 years of age or older (OR, 2.1 [CI, 1.2 to 3.6]) compared with patients 50 to 59 years of age. Patients 80 years of age or older stayed an average of 1 day more in the hospital, after adjustment for other clinical data (P = 0.001). CONCLUSIONS: Elderly patients had a higher rate of major perioperative complications and mortality after noncardiac surgery and a longer length of stay, but even in patients 80 years of age or older, mortality was low.

Modulation of B-cell proliferative response by a soluble extract of Nippostrongylus brasiliensis.

We and others have previously shown that nematodes or nematode products can stimulate or inhibit the generation of lymphocyte responses, suggesting that nematodes exert diverse effects on the developing immune responses of their host. In this study we examined the immunomodulatory effect of a soluble extract of Nippostrongylus brasiliensis (adult worm homogenate [AWH]) on B-cell responsiveness. We found that the extract inhibited the proliferation of B cells to lipopolysaccharide (LPS) stimulation in a dose-dependent manner. This effect was specific to B cells, since the extract did not inhibit T-cell proliferation to concanavalin A or anti-CD3 stimulation. The data presented here confirm that the extract is not toxic to B cells. We present evidence that the active factor is proteinaceous in nature and that the inhibitory activity is restricted to the adult stage of Nb. The extract does not appear to interfere with early activation events since it can be added up to 48 h after LPS stimulation, and it inhibited responses to phorbol myristate acetate and ionomycin. Furthermore, the proliferation of B cells to other activators was also inhibited by AWH. This observation shows that the inhibitory activity of AWH is not restricted to LPS-mediated B-cell proliferation. We present evidence that, in the absence of accessory cells, the inhibitory effect of the extract was ablated. This observation shows that the activity of AWH is not mediated directly on B cells but is mediated via the production of negative signals from accessory cells (macrophages), which affect a downstream pathway required by all B-cell activators tested. These effects on B-cell and accessory cell function are likely to have a significant effect on the outcome of infections experienced concurrently.

Extract of Nippostrongylus brasiliensis stimulates polyclonal type-2 immunoglobulin response by inducing De novo class switch.

Infection with the nematode parasite Nippostrongylus brasiliensis induces a pronounced type-2 T-cell response that is associated with marked polyclonal immunoglobulin E (IgE) and IgG1 production in mice. To examine the differential roles of the infection and products produced by nematodes, we investigated a soluble extract of N. brasiliensis for the ability to mediate this type-2 response. We found that the extract induced a marked increase in IgE and IgG1 levels, similar to that induced by the infection. The extract did not affect the level of IgG2a in serum, showing that the effect was specific to IgE and IgG1 (type-2-associated immunoglobulin) rather than inducing a nonspecific increase in all immunoglobulin isotypes. This response was also associated with increased interleukin-4 production in vitro. These results confirm that the extract, like infection, is a strong inducer of polyclonal type-2 responses and a reliable model for investigating the regulation of nematode-induced responses. The extract induced the production of IgG1 when added to in vitro cultures of lipopolysaccharide-stimulated B cells. This provides evidence for the induction of class switch. It did not induce upregulation of IgG1 in naive (unstimulated) B cells or expand B cells in in vitro cultures. Analysis of DNA from the spleens of mice treated with the extract by digestion-circularization PCR demonstrated a marked increase in the occurrence of gamma1 switch region gene recombination in the cells in vivo. These results provide strong evidence that soluble worm products are able to mediate the marked polyclonal gamma1/epsilon response and that infection is not required to mediate this response. Furthermore, these data provide evidence that the soluble nematode extract induces this effect by causing de novo class switch of B cells and not by an expansion of IgG1 B cells or an increase in antibody production by IgG1 plasma cells.