scholarly journals Serum Bactericidal Assays To Evaluate Typhoidal and Nontyphoidal Salmonella Vaccines

2014 ◽  
Vol 21 (5) ◽  
pp. 712-721 ◽  
Author(s):  
Mary Adetinuke Boyd ◽  
Sharon M. Tennant ◽  
Venant A. Saague ◽  
Raphael Simon ◽  
Khitam Muhsen ◽  
...  
Keyword(s):  
Sub Saharan Africa ◽  
Content Type ◽  
Vaccine Candidates ◽  
Live Attenuated Vaccines ◽  
Bactericidal Antibody ◽  
Paratyphi B ◽  
Sub Saharan ◽  
Functional Antibodies ◽  
New Vaccines

ABSTRACTInvasiveSalmonellainfections for which improved or new vaccines are being developed include enteric fever caused bySalmonella entericaserovars Typhi, Paratyphi A, and Paratyphi B and sepsis and meningitis in young children in sub-Saharan Africa caused by nontyphoidalSalmonella(NTS) serovars, particularlyS. entericaserovars Typhimurium and Enteritidis. Assays are needed to measure functional antibodies elicited by the new vaccines to assess their immunogenicities and potential protective capacities. We developedin vitroassays to quantify serum bactericidal antibody (SBA) activity induced byS. Typhi,S. Paratyphi A,S. Typhimurium, andS. Enteritidis vaccines in preclinical studies. Complement from various sources was tested in assays designed to measure antibody-dependent complement-mediated killing. Serum from rabbits 3 to 4 weeks of age provided the best complement source compared to serum from pigs, goats, horses, bovine calves, or rabbits 8 to 12 weeks of age. ForS. Enteritidis,S. Typhimurium, andS. Typhi SBA assays to be effective, bacteria had to be harvested at log phase. In contrast,S. Paratyphi A was equally susceptible to killing whether it was grown to the stationary or log phase. The typhoidal serovars were more susceptible to complement-mediated killing than were the nontyphoidal serovars. Lastly, the SBA endpoint titers correlated with serum IgG anti-lipopolysaccharide (LPS) titers in mice immunized with mucosally administeredS. Typhimurium,S. Enteritidis, andS. Paratyphi A but notS. Typhi live attenuated vaccines. The SBA assay described here is a useful tool for measuring functional antibodies elicited bySalmonellavaccine candidates.

scholarly journals Sulfamethoxazole Susceptibility of Mycobacterium tuberculosis Isolates from HIV-Infected Ugandan Adults with Tuberculosis Taking Trimethoprim-Sulfamethoxazole Prophylaxis

2015 ◽  
Vol 59 (9) ◽  
pp. 5844-5846 ◽  
Author(s):  
Sam Ogwang ◽  
Caryn E. Good ◽  
Brenda Okware ◽  
Mary Nsereko ◽  
Michael R. Jacobs ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Multidrug Resistant ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Pulmonary Tb ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Sub Saharan

ABSTRACTAdditional drugs are needed for the treatment of multidrug-resistant tuberculosis (TB). Sulfamethoxazole has been shown to havein vitroactivity againstMycobacterium tuberculosis; however, there is concern about resistance given the widespread use of trimethoprim-sulfamethoxazole prophylaxis among HIV-infected patients in sub-Saharan Africa. Thirty-eight of 40Mycobacterium tuberculosisisolates (95%) from pretreatment sputum samples from Ugandan adults with pulmonary TB, including HIV-infected patients taking trimethoprim-sulfamethoxazole prophylaxis, were susceptible with MICs of ≤38.4 μg/ml.

scholarly journals Opsonophagocytic Assay To Evaluate Immunogenicity of Nontyphoidal Salmonella Vaccines

2016 ◽  
Vol 23 (6) ◽  
pp. 520-523 ◽  
Author(s):  
Girish Ramachandran ◽  
Mary Adetinuke Boyd ◽  
Jennifer MacSwords ◽  
Ellen E. Higginson ◽  
Raphael Simon ◽  
...  
Keyword(s):  
Sub Saharan Africa ◽  
Morbidity And Mortality ◽  
Content Type ◽  
Killing Assay ◽  
Invasive Infections ◽  
Sub Saharan ◽  
Functional Antibodies ◽  
Opsonophagocytic Killing ◽  
Rabbit Complement

ABSTRACTNontyphoidalSalmonella(NTS) invasive infections are an important cause of morbidity and mortality in sub-Saharan Africa. Several vaccines are in development to prevent these infections. We describe an NTS opsonophagocytic killing assay that uses HL-60 cells and baby rabbit complement to quantify functional antibodies elicited by candidate NTS vaccines.

scholarly journals Physiological Differences in Cryptococcus neoformans Strains In Vitro versus In Vivo and Their Effects on Antifungal Susceptibility

2016 ◽  
Vol 61 (3) ◽  
Author(s):  
Nina T. Grossman ◽  
Arturo Casadevall
Keyword(s):  
Cryptococcus Neoformans ◽  
Cryptococcal Meningitis ◽  
Antifungal Susceptibility ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Laboratory Conditions ◽  
Physiological Differences ◽  
Sub Saharan

ABSTRACT Cryptococcus neoformans is an environmentally ubiquitous fungal pathogen that primarily causes disease in people with compromised immune systems, particularly those with advanced AIDS. There are estimated to be almost 1 million cases per year of cryptococcal meningitis in patients infected with human immunodeficiency virus, leading to over 600,000 annual deaths, with a particular burden in sub-Saharan Africa. Amphotericin B (AMB) and fluconazole (FLC) are key components of cryptococcal meningitis treatment: AMB is used for induction, and FLC is for consolidation, maintenance and, for occasional individuals, prophylaxis. However, the results of standard antifungal susceptibility testing (AFST) for AMB and FLC do not correlate well with therapeutic outcomes and, consequently, no clinical breakpoints have been established. While a number of explanations for this absence of correlation have been proffered, one potential reason that has not been adequately explored is the possibility that the physiological differences between the in vivo infection environment and the in vitro AFST environment lead to disparate drug susceptibilities. These susceptibility-influencing factors include melanization, which does not occur during AFST, the size of the polysaccharide capsule, which is larger in infecting cells than in those grown under normal laboratory conditions, and the presence of large polyploid “titan cells,” which rarely occur under laboratory conditions. Understanding whether and how C. neoformans differentially expresses mechanisms of resistance to AMB and FLC in the AFST environment compared to the in vivo environment could enhance our ability to interpret AFST results and possibly lead to the development of more applicable testing methods.

scholarly journals In Vitro, Ex Vivo, and In Vivo Activities of Diamidines against Trypanosoma congolense and Trypanosoma vivax

2017 ◽  
Vol 61 (5) ◽  
Author(s):  
Kirsten Gillingwater ◽  
Christina Kunz ◽  
Christiane Braghiroli ◽  
David W. Boykin ◽  
Richard R. Tidwell ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Trypanosoma Congolense ◽  
Tsetse Fly ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Lead Compounds ◽  
Single Bolus Dose ◽  
Sub Saharan

ABSTRACT African animal trypanosomosis (AAT) is caused by the tsetse fly-transmitted protozoans Trypanosoma congolense and T. vivax and leads to huge agricultural losses throughout sub-Saharan Africa. Three drugs are available to treat nagana in cattle (diminazene diaceturate, homidium chloride, and isometamidium chloride). With increasing reports of drug-resistant populations, new molecules should be investigated as potential candidates to combat nagana. Dicationic compounds have been demonstrated to have excellent efficacy against different kinetoplastid parasites. This study therefore evaluated the activities of 37 diamidines, using in vitro and ex vivo drug sensitivity assays. The 50% inhibitory concentrations obtained ranged from 0.007 to 0.562 μg/ml for T. congolense and from 0.019 to 0.607 μg/ml for T. vivax. On the basis of these promising results, 33 of these diamidines were further examined using in vivo mouse models of infection. Minimal curative doses of 1.25 mg/kg of body weight for both T. congolense- and T. vivax-infected mice were seen when the diamidines were administered intraperitoneally (i.p.) over 4 consecutive days. From these observations, 15 of these 33 diamidines were then further tested in vivo, using a single bolus dose for administration. The total cure of mice infected with T. congolense and T. vivax was seen with single i.p. doses of 5 and 2.5 mg/kg, respectively. This study identified a selection of diamidines which could be considered lead compounds for the treatment of nagana.

scholarly journals Live Oral Salmonella enterica Serovar Typhi Vaccines Ty21a and CVD 909 Induce Opsonophagocytic Functional Antibodies in Humans That Cross-React withS. Paratyphi A andS. Paratyphi B

2014 ◽  
Vol 21 (3) ◽  
pp. 427-434 ◽  
Author(s):  
Rezwanul Wahid ◽  
Shah J. Zafar ◽  
Monica A. McArthur ◽  
Marcela F. Pasetti ◽  
Myron M. Levine ◽  
...  
Keyword(s):  
Salmonella Enterica ◽  
Content Type ◽  
Before And After ◽  
Human Sera ◽  
Antibody Titers ◽  
Paratyphi B ◽  
Iga Antibody ◽  
Functional Antibodies ◽  
New Generation

ABSTRACTLive oralSalmonella entericaserovar Typhi vaccine Ty21a induces specific antibodies that cross-react againstSalmonella entericaserovar Paratyphi A andSalmonella entericaserovar Paratyphi B, although their functional role in clearance remains unknown. We utilized anin vitroassay with THP-1 macrophages to compare the phagocytosis and survival ofSalmonellaopsonized with heat-inactivated human sera obtained before and after vaccination with Ty21a or a live oralS. Typhi vaccine, CVD 909. Opsonization with postvaccination sera predominantly increased the phagocytosis ofS. Typhi relative to the corresponding prevaccination sera, and increases were also observed withS. Paratyphi A andS. Paratyphi B, albeit of lower magnitudes. Relative to prevaccination sera, opsonization with the postvaccination sera reduced the survival inside macrophages ofS. Typhi but not ofS. Paratyphi A orS. Paratyphi B. Higher anti-S. Typhi O antigen (lipopolysaccharide [LPS]) IgG, but not IgA, antibody titers correlated significantly with postvaccination increases in opsonophagocytosis. No differences were observed between immunization with four doses of Ty21a or one dose of CVD 909. Ty21a and CVD 909 induced cross-reactive functional antibodies, predominantly againstS. Typhi. IgG anti-LPS antibodies may be important in phagocytic clearance of these organisms. Therefore, measurement of functional antibodies might be important in assessing the immunogenicity of a new generation of typhoid and paratyphoid A vaccines. (The CVD 909 study has been registered at ClinicalTrials.gov under registration no. NCT00326443.)

scholarly journals Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model

2017 ◽  
Vol 61 (7) ◽  
Author(s):  
Chunxia Zhao ◽  
Manjula Gunawardana ◽  
Francois Villinger ◽  
Marc M. Baum ◽  
Mariana Remedios-Chan ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Sub Saharan Africa ◽  
Release Rates ◽  
Content Type ◽  
Macaque Model ◽  
Intravaginal Rings ◽  
Broadly Neutralizing Antibody ◽  
Sub Saharan ◽  
Hiv 1

ABSTRACT The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known human immunodeficiency virus type 1 (HIV-1) isolates in vitro, is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other underdeveloped regions may be limited by the high cost of conventionally produced antibodies and the limited capacity to manufacture such antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering Nicotiana-manufactured VRC01 (VRC01-N) over a range of release rates have been developed. The pharmacokinetics and preliminary safety of VRC01-N pod-IVRs were evaluated in a rhesus macaque model. The devices sustained VRC01-N release for up to 21 days at controlled rates, with mean steady-state VRC01-N levels in vaginal fluids in the range of 102 to 103 μg g−1 being correlated with in vitro release rates. No adverse safety indications were observed. These findings indicate that pod-IVRs are promising devices for the delivery of the candidate topical microbicide VRC01-N against HIV-1 infection and merit further preclinical evaluation.

scholarly journals Schistosoma mansoni eggs induce Wnt/β-catenin signaling and activate the protooncogene c-Jun in human and hamster colon

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jakob Weglage ◽  
Friederike Wolters ◽  
Laura Hehr ◽  
Jakob Lichtenberger ◽  
Celina Wulz ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Colorectal Carcinogenesis ◽  
Sub Saharan Africa ◽  
Interleukin 4 ◽  
Health Burden ◽  
Sub Saharan ◽  
Considerable Morbidity ◽  
First Time

AbstractSchistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic flatworms of the genus Schistosoma, with considerable morbidity in parts of the Middle East, South America, Southeast Asia, in sub-Saharan Africa, and particularly also in Europe. The WHO describes an increasing global health burden with more than 290 million people threatened by the disease and a potential to spread into regions with temperate climates like Corsica, France. The aim of our study was to investigate the influence of S. mansoni infection on colorectal carcinogenic signaling pathways in vivo and in vitro. S. mansoni infection, soluble egg antigens (SEA) and the Interleukin-4-inducing principle from S. mansoni eggs induce Wnt/β-catenin signaling and the protooncogene c-Jun as well as downstream factor Cyclin D1 and markers for DNA-damage, such as Parp1 and γH2a.x in enterocytes. The presence of these characteristic hallmarks of colorectal carcinogenesis was confirmed in colon biopsies from S. mansoni-infected patients demonstrating the clinical relevance of our findings. For the first time it was shown that S. mansoni SEA may be involved in the induction of colorectal carcinoma-associated signaling pathways.

Cross-cultural communication imperatives

2018 ◽  
Vol 14 (2/3) ◽  
pp. 170-187 ◽  
Author(s):  
James Baba Abugre
Keyword(s):  
Business Environment ◽  
Cross Cultural ◽  
Sub Saharan Africa ◽  
Work Outcomes ◽  
Cultural Communication ◽  
Global Business ◽  
Content Type ◽  
Local Staff ◽  
Cross Cultural Communication ◽  
Sub Saharan

Purpose Given the rising expansion of Western multinational companies (MNCs) to the African contexts, the development of expatriates and local employees has become increasingly important to the human resource management of these MNCs. This paper aims to provide critical lessons on cross-cultural communication competences for Western expatriates working in the sub-Saharan Africa business environment. Design/methodology/approach This paper is a qualitative phenomenology that makes use of lived experiences of senior expatriate staff working in Ghana in the form of direct interviews. Findings Results showed that cross-cultural communication competence is very important for Western expatriates’ functioning in sub-Saharan Africa. The findings also established a plethora of cross-cultural communication skills that are essential for Western expatriates’ successful adaptation and work outcomes in Africa. Practical implications This research argues that there is the need for the appreciations of the differing cultural patterns of expatriates and local staff, and this provides the underlying assumptions of intercultural and cross-cultural communication in global business. Originality/value A critical perspective of international business that has scarcely been studied offers lessons for Western expatriates working in sub-Saharan Africa.

A comparison of global suicide terrorism by region before and after 9/11 terrorist attacks

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Ahmet Guler ◽  
Mustafa Demir
Keyword(s):  
Time Series ◽  
Interrupted Time Series ◽  
Sub Saharan Africa ◽  
Terrorist Attacks ◽  
Suicide Terrorism ◽  
Content Type ◽  
The World ◽  
Before And After ◽  
Sub Saharan ◽  
Global Terrorism Database

Purpose This study aims to examine the effect of the 9/11 terrorist attacks on suicide terrorism in different regions of the world and changes in the trends in suicide terrorism according to regions before and after 9/11. Design/methodology/approach Using the data obtained from the Global Terrorism Database from 1981 to 2019, the descriptive statistics were computed first and then, independent samples t-tests were run to compare the monthly mean percentage of suicide-terrorism incidents that occurred in each region between the pre-9/11 and the post-9/11 periods. Finally, to statistically assess the effect of the 9/11 attacks and changes in the trends for the dependent variables over time, monthly interrupted time-series analyzes were conducted. Findings The results of monthly interrupted time series analyzes showed that after the 9/11 attacks, the trends for suicide-terrorism rates decreased significantly in three regions including South Asia, the Middle East and North Africa and Europe, while the trend for suicide-terrorism rates increased significantly in Sub-Saharan Africa. However, no statistically significant changes in the trends in suicide-terrorism rates occurred in three regions including North America, East Asia and Central Asia and Southeast Asia before 9/11, during November 2001 or after 9/11. Originality/value This study indicates the critical importance of the 9/11 terrorist attacks in suicide terrorism and its impact on these events in different regions of the world. The research also provides some recommendations concerning the effectiveness of defensive and offensive counterterrorism policies against suicide terrorism.

Factors limiting the adoption of hemp as an alternative sustainable material for green building delivery in Ghana

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Kofi Agyekum ◽  
Emmanuel Adinyira ◽  
James Anthony Oppon
Keyword(s):  
Building Materials ◽  
Green Building ◽  
Sub Saharan Africa ◽  
Content Type ◽  
Sustainable Material ◽  
Environmental Threats ◽  
Additional Information ◽  
Comparative Review ◽  
Sub Saharan ◽  
The Government

PurposeThe increased awareness of global environmental threats like climate change has created an upsurge of interest in low embodied carbon building materials for green building delivery. Though the literature advocates for the use of hemp-based building materials, there is no evidence of studies to explore its potential use in Ghana. Therefore, this study explores the potential factors that limit the adoption of hemp as an alternative sustainable material for green building delivery in Ghana.Design/methodology/approachA structured questionnaire was used to solicit the views of built environment professionals operating in construction, consulting and developer firms. The questions were developed through a comparative review of the related literature and complemented with a pilot review. Data were analysed via descriptive and inferential statistics.FindingsOn the average, the majority of the respondents showed a moderate level of awareness of hemp and its related uses in the construction industry. Also, certain key factors like the perceived association of hemp with marijuana, lack of expertise in the production of hemp-related building materials, farmers not getting the needed clearance for the cultivation of hemp, lack of legislation by the government in the legalisation of hemp and the inadequate knowledge of consumers on the benefits of hemp-based building materials were identified as potential limitations to the adoption of hemp as an alternative sustainable material for green building delivery.Originality/valueThe findings from this study provide insights into a less investigated area in sub-Saharan Africa and further provide new and additional information to the current state-of-the-art on the potential for the use of hemp in the building construction sector.

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