Outcomes of daratumumab in the treatment of multiple myeloma: A retrospective cohort study from the Canadian Myeloma Research Group Database.

Daratumumab (dara) has significantly altered the therapeutic landscape of multiple myeloma (MM), especially in the relapsed setting. This study aimed to evaluate the outcomes of dara-containing regimens in the Canadian real-world setting among relapsed and refractory MM available within the national Canadian Myeloma Research Group Database (CMRG-DB). A total of 583 MM patients who received dara-based therapy in second-line or later treatment were included. After a median follow-up of 17.5 months, the median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 13.1 and 32.9 months, respectively. The median PFS and OS were 23.5 and 49.1 months in second-line treatment and decreased to 12.8 and 43.0 months in third-line and 7.0 and 20.5 months in fourth-line treatment respectively. Dara in monotherapy with or without corticosteroids after a median of four prior lines of therapy resulted in a median PFS of 3.9 months and a median OS of 17.1 months. The addition of bortezomib, lenalidomide or pomalidomide to dara resulted in an improved median PFS and OS of 8.3 and 26.2 months; 26.8 and 43.0 months; and 9.7 and 31.4 months respectively. These retrospective data from the CMRG-DB suggest that outcomes are superior when dara is used in combination and in earlier lines of treatment.

Epidemiological situation of transboundary animal diseases in North African countries-proposition of a regional control strategy.

The Food and Agricultural Organization (FAO) defined transboundary animal diseases (TADs) as those that are of significant economic, trade, and food security importance for a considerable number of countries. TADs can easily spread to other countries, reach epidemic proportions, and where control, management, or exclusion is required cooperation between several countries. The North African countries are vulnerable to several TADs by virtue of its geographical location, its borders with the Sahel region, and peculiar control constraints on the budgets of the national veterinary services of each country and on the livelihoods of livestock owners across the region. In a narrative approach, we comprehensively described the epidemiology of TADs in North African countries, eradication constraints and control measures adopted to conclude with a proposition of a regional control strategy. Our review uncovered foot-and-mouth disease, peste des petites ruminants, bluetongue, sheep/goats pox, brucellosis, West Nile and Rift Valley fever, as the major TADs in this region, while the major constraints identified were illegal animal movement, communal clashes, unreported outbreaks, poor vaccination coverage, and other factors peculiar to each etiology. Therefore, the establishment of early warning systems and proper implementation of control measures at regional level are highly recommended to the relevant stakeholders involved in TADs control in the region.

The epidemiology of cattle abortion in Algeria.

In Algeria, the epidemiology of cattle abortions is not well understood. Therefore, the present study aims to estimate the prevalence of abortion in 75 Algerian cattle herds and correlate its possible association with brucellosis positivity and some managerial risk factors. The cattle abortion herd prevalence was 41.33% [95% CI 30.16-52.5%]. As for brucellosis, the serological evidence of brucellosis exposure was observed in 9 out of 75 herds accounting for 12% [95% CI 4.65-19.35] herd seroprevalence. The risk factor analysis using the univariable analysis followed by multivariable logistic regression did confirm that brucellosis positivity (OR = 5.19), mixed herd (OR = 2.5), contact with other herd (OR = 2.91), presence of dog in the herd (OR = 2.89), imported cattle (OR = 1.91), and farmers with less than 2 years' experience (OR = 2.69) as risk factors for abortion in Algerian cattle herds. Targeting these factors using a comprehensive control measure is needed to improve animal welfare and reduce economic losses associated with abortion in dairy cattle.

Prevalence, distribution, and risk factor for sheep pox and goat pox (SPGP) in Algeria.

A cross-sectional study using a tested questionnaire was carried out across Algeria between January and June 2014. Our investigation demonstrated that of the 150 flocks visited, 21 were positive for sheep pox and goat pox (SPGP) with an overall flock prevalence of 14% (95% CI 11.08-16.92%) suggesting that SPGP is endemic in Algeria. Our results showed also that the disease appears only in sheep and no case affecting goats has been reported. For the risk factor analysis, univariate analysis of variables followed by a multiple logistic regression identified steppe region (OR = 1.81, 95% CI 0.87-2.57; P = 0.037), large flocks (OR = 2. 19, 95% CI 1.02-3.36; P = 0.027), and transhumance (OR = 3.98, 95% CI 2.59-5.34; P = 0.021) as risk factors in the spread of the disease. Furthermore, our study revealed that the use of vaccination as preventive measures in the selected flocks decreased the odds for SPGP positivity by 5.78 (95% CI 2.22-9.34; P < 0.001) times compared to non vaccinated flocks. In conclusion, our findings documented an evidence of a widespread distribution and endemic establishment of the SPGP in Algerian sheep population despite the annual vaccination program. Consequently, the vaccination must cover all the Algerian sheep population to improve animal welfare and reduce economic losses associated with outbreak episodes.

Foot-and-mouth disease (FMD) in the Maghreb and its threat to southern European countries.

Foot-and-mouth disease (FMD) is a highly contagious and transboundary viral disease of domesticated and wild cloven-hoofed animals. The present study summarizes the knowledge generated from the epidemiology, diagnosis, and surveillance of the disease in the Maghreb (2014-2015) in assessing its threat to southern European countries. Currently, two serotypes of the FMD virus (O and SAT-2) and four lineages are circulating in the Maghreb region. The introduction of serotype SAT-2 in Libya and Mauritania in 2012 and 2015 respectively sets their neighbors and subsequently south European countries at constant risk of FMD re-emergence. The potential pathways of FMD introduction to southern European countries from the Maghreb are the illegal introduction of infected animals and animal products, particularly meat or meat products carried by refugees.

Did Rev-1 small ruminants vaccination helped improve cattle brucellosis prevalence status in Algeria?

In 2006, the Algerian authorities started the Rev-1 vaccination of sheep and goats; consequently, there was a significant improvement of small ruminant brucellosis sanitary status. In this paper, we attempt to study the effect of Rev-1 small ruminants' vaccination on cattle brucellosis prevalence in Algeria. Our results showed an overall cattle herd seroprevalence of 12% (9 positive herds of 75). The risk factor analysis using a logistic regression model indicated that the presence of small ruminants along with cattle in the herd (mixed herds) decreased the odds for brucellosis seropositivity by 1.69 [95% CI 0.54-2.84; P = 0.042] compared to the cattle herds only. Likewise, the present study showed that the presence of Rev-1 vaccinated small ruminants in the herd decreased also the odds for brucellosis seropositivity by 4.10 [95% CI 3.20-5.00; P = 0.003] compared to other herds. This result lead to the assumption that the small ruminants Rev-1 vaccination diminish Brucella microbisme pressure in the mixed herds and help decrease the cattle brucellosis prevalence in these herds.

First serological and molecular evidence of PPRV occurrence in Ghardaïa district, center of Algeria.

In February 2012, an outbreak of peste des petits ruminants (PPR) was suspected in Ghardaïa district at the center of Algeria. Clinical, serological, and molecular investigations were performed to confirm the occurrence of PPRV. The overall morbidity, mortality, and case fatality rates of the ten flocks investigated were 12.2, 2.5, and 20.3 %, respectively. At the flock level, positivity to PPR was 100, 90, and 100 % by competitive ELISA (c-ELISA), RT-PCR of blood samples, and oculo-nasal swabs, respectively. At the individual levels, the present study showed that out of 186 samples collected from the same animals 17/62 (27.41 %), 14/62 (22.85 %), and 36/62 (58.06 %) were positive by c-ELISA, RT-PCR of blood samples, and RT PCR of oculo-nasal swabs, respectively. The positivity of PPR was significantly higher using RT-PCR of oculo-nasal swabs than c-ELISA and RT-PCR of blood samples. The N gene partial sequence of five PPRV-positive amplicons revealed 100 % homology among them and phylogenetically belonged to lineage IV. The sequences also showed similarity range of 97-99 % with the strains implicated in the Moroccan and Tunisian outbreaks, however, suggesting that a similar strain is circulating across this area of the Maghreb and highlighting the need for a regional control approach.

Real-world data on lenalidomide dosing and outcomes in patients newly diagnosed with multiple myeloma: Results from the Canadian Myeloma Research Group Database.

Using the Canadian Myeloma Research Group Database, a retrospective study of 167 newly diagnosed, transplant-ineligible patients with multiple myeloma (MM) that received lenalidomide-dexamethasone as front-line treatment was conducted to understand the impact of lenalidomide dosing. Starting dose modifications were common, 42% of patients started on lenalidomide <25 mg with normal renal function. During treatment course, 35% of patients required further dose reduction. Dose reductions in the first year did not have an impact on progression free survival or overall survival. Further studies need to be conducted to understand the impact of dosing strategies of anti-MM agents in the real world.

Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database.

BACKGROUND: Considerable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization. METHODS: The Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018. RESULTS: A total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment. CONCLUSION: We present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.

Sequential Use of Carfilzomib and Pomalidomide in Relapsed Multiple Myeloma: A Report from the Canadian Myeloma Research Group (CMRG) Database.

The treatment of multiple myeloma has dramatically improved due to the availability of novel therapies that are highly effective and are quickly moving into first-line therapy. The Canadian Agency for Drugs and Technologies in Health (CADTH) recently recommended that patients who receive daratumumab should only be eligible to receive either carfilzomib or pomalidomide but not both, for relapsed MM. In order to assess the efficacy of these two agents in the relapsed setting, we utilized our national myeloma database. A total of 121 patients were reviewed, 49 patients received CAR- before POM-based (CAR-POM), and 73 patients received POM- before CAR-based (POM-CAR) therapy. In the groups selected, the median PFS was 4.93 months (95% CI, 2.76-7.07) and 5.36 months (95% CI, 3.75-6.94) for CAR-POM and POM-CAR, respectively. The median OS for patients treated with CAR-POM was 11.01 months (95% CI, 4.50-19.13), and for patients treated with POM-CAR the median OS was 10.98 months (95% CI, 8.98-19.17). In this real-world observational study, we demonstrated that both CAR- and POM-based therapies, irrespective of the order in which they were used, were effective treatment options for patients with advanced relapsed MM.

Efficacy of Daratumumab-Containing Regimens Among Patients With Multiple Myeloma Progressing on Lenalidomide Maintenance: Retrospective Analysis.

BACKGROUND: Daratumumab, a monoclonal antibody directed against CD38 is a recent class of drugs introduced into the multiple myeloma therapeutic landscape. While clinical trial data have shown a remarkable impact on outcomes, the efficacy of daratumumab combination therapies in specific clinically relevant subgroups including among patients refractory to lenalidomide maintenance remains unknown. METHODS: In this study, retrospective data were reviewed from the Canadian Myeloma Research Group and the German Munster Myeloma databases to identify patients that received daratumumab in combination with pomalidomide (DPd), lenalidomide (DRd), and bortezomib (DVd) in a population that had relapsed on lenalidomide maintenance postautologous stem cell transplant. The primary aim of the study was to look at outcomes of these patients in different daratumumab combinations. RESULTS: A total of 73 patients were identified. The median age of the patients at the time of daratumumab initiation was 60 (38-72) and 64.4% (n = 47) were men. In the selected cohort, 43.8% (n = 32) were treated with DRd, 31.5% (n = 23) with DVd, and 24.7% (n = 18) with DPd regimen. The median progression-free survival (PFS) of the entire cohort was 15.8 months (95% CI, 12.9-37.1 months). The median PFS of the individual regimens was as follows: DPd 18.9 months (95% CI, 13.7-not reached), DRd 21.7 months (95% CI, 11.6-not reached), and DVd 12.9 months (95% CI, 3.1-not reached). CONCLUSIONS: Daratumumab-containing therapies are effective regimens in patients progressing on lenalidomide maintenance. Additional studies are required to decide the optimal regimen post-lenalidomide maintenance.

Carfilzomib usage patterns and outcomes in patients with relapsed multiple myeloma: A multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.

Carfilzomib is an active and commonly used treatment in patients with multiple myeloma (MM). Using the Canadian Myeloma Research Group Database, we performed a retrospective observational study of patients treated with carfilzomib for relapse of MM in a real-world setting in Canada between years 2007 and 2020. A total of 445 patients were included in this study: the doublet (Kd/p, n = 218) and triplets (KCd, n = 88; KRd, n = 99; KPd/p, n = 40). One hundred and twenty-two (27%) received carfilzomib-based treatment in line 2, 133 (30%) in line 3, 90 (20%) in line 4, and 100 (23%) in line 5 or higher. Carfilzomib was dosed weekly in 40% of patients and twice weekly in 60%. The overall response rate of the entire cohort was 57.7%, with 33.6% of patients achieving very good partial response or better. Median progression-free survival for the overall cohort was 6.3 months with overall survival 19.7 months. This study provides a benchmark for carfilzomib-based regimens in the real world, demonstrating that these regimens are effective in treating patients with relapsed MM.

Occurrence and seasonal variation of aflatoxin M1 in raw cow milk collected from different regions of Algeria.

BACKGROUND AND AIM: Aflatoxins are metabolites of molds that exert potentially toxic effect on animals and humans. This study aimed to investigate the occurrence of aflatoxin M1 (AFM1) in raw cow milk collected during 1 year (2016-2017) from different regions of Algeria and risk factors associated with the contamination. MATERIALS AND METHODS: During the survey period, 84 samples of raw milk were collected in three regions of Algeria (northeast, north center, and northwest) during four seasons. AFM1 levels were analyzed by competitive enzyme-linked immunosorbent assay. RESULTS: AFM1 was detected in 39 (46.43%) samples (total mean concentration, 71.92 ng/L; range, 95.59-557.22 ng/L). However, the AFM1 levels exceeded the maximum tolerance limit set by the Food and Drug Administration in the USA (500 ng/L) in only 1 sample (1.19%). Statistical analysis revealed significant differences (p˂0.005) between AFM1 levels in milk samples collected in the spring and autumn. The mean AFM1 levels in samples collected in the spring were significantly higher than those in samples collected in autumn. CONCLUSION: The survey indicates that farmers involved in milk production should be made aware of the adverse effects of aflatoxin contamination in animal feed. A systematic control program of supplementary feedstuff for lactating cows should be introduced by the public health authorities.

Epidemiology of dog-mediated zoonotic diseases in Algeria: a One Health control approach.

Globally, human-dog interactions cause significant social, economic and human health costs. Public health problems linked with dogs include mainly zoonotic diseases. Recently the concept of a global and integrative approach to improve the health and well-being of people, animals and the environment has been strongly endorsed. This concept, often referred to as One Health, also reflects the collaboration in the field of surveillance and monitoring. Because humans and animals often suffer from the same pathogens and share the same environment, a cross-sector approach integrating human and animal disease surveillance information is required. The aims of the present study were to describe the incidence of dog-mediated zoonotic diseases in Algeria between 2010 and 2017, and to propose a One Health approach to control these diseases in Algeria. Rabies, leishmaniasis and echinococcosis are the major zoonoses in Algeria, with a reported average number of deaths per year, respectively, of 18, 7947 and 387. These zoonoses occur with the uncontrolled proliferation of household waste deposits, particularly in and around urban area which maintain the presence of stray dogs. The persistence of these diseases indicates the need for greater partnership and collaboration among multiple sectors, including medical doctors, veterinarians, ecologists, environmentalists and law-enforcement agents. Such partnerships permit the sharing of information, facilities and resources under a One Health approach; permit rapid communication among disciplines as well as interdisciplinary training/education opportunities and raising awareness among human population; and allow a combined effort towards disease surveillance/control, which will consequently improve the efficiency of the control programmes.

Understanding the epidemiology of sheep-pox outbreaks among vaccinated Algerian sheep and post vaccination evaluation of the antibodies kinetics of the commercially used vaccine.

Sheep pox is a disease of veterinary concern to small ruminant producers and veterinary diagnosticians, because of the associated tangible economic losses. The epidemiological analysis of sheep pox, among vaccinated sheep flock in Algeria from 2007 to 2016, showed that the disease outbreaks occurred every year and across all Algeria region with an average of 44.9 outbreaks per year, these outbreaks correlate with the region climate, the flocks' density and the transhumance practices. The one-year post vaccination antibody kinetics evaluation study of the commercially used vaccine in Algeria demonstrated a mild humoral response, the neutralization index range between 0.73 and 1.22. Therefore, the present study recommends a challenge study, using a virulent local strain, to evaluate the vaccine efficacy. Furthermore, quality control approach for the vaccine production processes is required.

History of Foot-and-mouth disease in North African countries.

Foot-and-mouth disease (FMD) is a highly infectious and contagious transboundary viral disease of domesticated and wild cloven-hoofed animals. Wide prevalence of FMD in Asia and Africa associated with huge economic losses to livestock farming and industry prompted global concern. The present review summarizes the state of the art research in epidemiology, diagnosis, and surveillance of FMD in the North African countries. Even if the situation varies across the North African states, FMD is still a key factor affecting livestock production in this part of the world. Historically, 4 serotypes have circulated in North Africa (O, A, SAT2, and C) with type O being the most prevalent serotype, followed by serotype A. However, the rapid spread of SAT2 lineages from Libya to Egypt in 2012 and the O lineages from Libya to Tunisia, Algeria, and Morocco between 2014 and 2015 demonstrated the need for a robust surveillance system to detect and respond effectively to exotic infections. Emergence and re-emergence of FMD virus genotypes/lineages have been detected engendering the need to replace vaccine strains quite frequently.

The epidemiology of dog rabies in Algeria: Retrospective national study of dog rabies cases, determination of vaccination coverage and immune response evaluation of three commercial used vaccines.

Rabies is a neglected zoonotic disease. Several animal species can transmit rabies, but domestic dogs are the main reservoir implicated in rabies transmission to human and other susceptible animals. There is a scarcity of data regarding canine rabies in Algeria. Hence, this report is the first study that attempts to understand the epidemiology of dog rabies through a retrospective national study of rabies cases between 2010 and 2016, determination of canine vaccination coverage and evaluation of immune response of three rabies commercial vaccines used in Algeria. Our results revealed the persistent nature of dog rabies in Algeria; with a mean of 131 positive cases per year. The vaccination coverage findings indicated that 30.81% (126/409) of the reported vaccinated dog and 47.98% (261/544) of all studied dogs presented low level of rabies antibodies titres (less than 0.5 IU), and were therefore considered not immune to rabies. Additionally, our vaccine evaluation findigs showed a weak immune response of inactivated vaccine without adjuvant. Even with adjuvanted inactivated and attenuated live vaccines, several vaccinated dogs did not develop vaccine protection. Therefore, our results recommend further studies to test the efficiency of adding a booster vaccine shot, especially in primo-vaccinated dogs to optimize the vaccination protocol; rabies is potentially fatal zoonosis, tolerating no vaccine failure. Moreover, the present study establish the necessity to re-examine the national rabies control program, implemented in 1996, particularly concerning population education, vaccination strategy, surveillance and campaigns monitoring.

Abortion and various associated risk factors in small ruminants in Algeria.

Identification of the causes of abortion among the huge population of small ruminants in Algeria (≈31 millions heads), is an important task for the control of livestock productivity and viability scourges to the small ruminants industry. Optimal production and utilization is constrained by a number of factors: disease, poor feeding and low management skills. Therefore, in the present study the prevalence of abortion in Algerian small ruminant's flocks was estimated and its possible association was correlated with infectious (PPR, BT and Brucellosis seropositivity) and managerial (flock size, grazing system, type of farming, and contact with other flocks) risk factors. The present study showed an overall flock prevalence of small ruminant's abortion as 75.33% (113/150) [95% CI 71.72-78.94%]. The risk factor analysis using multivariable logistic regression recognized the north-western and the steppe region as well as PPR positivity as a risk factor for abortion in Algerian small ruminant's flocks. The odds of flock abortion was 11.47 [95% CI 2.39-54.88; P=0.002] and 10.31 [95% CI 1.28-82.88; P=0.028] times higher in north-western and steppe regions respectively compared to other region. Also the presence of PPRV infection in small ruminant flocks amplified the odds by 6 times [95% CI 2.221-17.427; P=0.001].Surprisingly, the univariate analysis for the other risk factors associated with abortions in Algerian small ruminant flocks indicated no statistically significant links with bluetongue (P=1.000) and brucellosis seropositivity (P=0.334). Flock size (P=0.574), type of farming (P=0.443), grazing system (P=0.117) and contact with other flocks (P=0.245) was also not statistically significant. Our results revealed that abortion in small ruminants is a challenge to farmers and PPR was chiefly linked to it. Therefore an effective vaccination and control programme is advocated for small ruminants in Algeria.

Seroprevalence, distribution and risk factor for peste des petits ruminants (PPR) in Algeria.

Peste des petit ruminants (PPR) is a highly contagious and infectious viral disease of small ruminants with severe socio-economic implications. The disease was first reported in the Southern part of Algeria in 2011 and by February 2012 it has reached the central part of the country. Estimating national prevalence, distribution and identification of risk factors remains a key component in understanding the epidemiology and control of the disease. The present study was carried out between January and June 2014, to include a detailed description of flock and within-flock seroprevalence and risk association between PPR seropositivity and various flock management factors in Algeria. A total of 150 flocks randomly sampled across the country were investigated and 4552 serum samples were collected from 3336 sheep and 1216 goats, respectively. C-ELISA was used to detect the presence of antibodies in small ruminant animals as an indicator of PPRV exposure. The results showed an overall true flock seroprevalence of 30.45% [95% CI 23.76-37.14] with a mean of the true within-flock prevalence as 29.87%±2.11. The mean of the true within-flock prevalence in mixed flocks (12.93%±1.85) was however found to be significantly higher than sheep flocks (5.74%±1.06). Also the mean of the true within-flock prevalence was found to be significantly higher in adult (35.36%±3.13) compared to young animals (21.83%±2.47) and in females (33.11%±2.87) compared to males (22.14%±2.31). The univariate analysis revealed that PPR overall flock seroprevalence was significantly higher (P<0.20) in large flock (50.61%) than in small flock (33.33%), in mixed flock (56.7%) than in sheep flock (35.35%) and in the flocks that had contact with other flocks (46.5%) compared to those who had not (30.6%). However the differences among studied regions and grazing system were not statistically significant. For the risk factor analysis, univariate analysis of variables followed by a multiple logistic regression identified mixed flocks [OR=2.64, 95% CI 1.30-5.38; P=0.007] and contact with other flocks [OR=2.27, 95% CI 0.99-5.21; P=0.053] as risk factors in the spread of the disease. In conclusion, this study revealed a high seroprevalence of PPR in Algerian small ruminants, therefore the establishment of early warning systems and comprehensive implementation of control measures are advocated to improve animal welfare and reduce economic losses.