Antimicrobial Peptides Therapy: An Emerging Alternative for Treating Drug-Resistant Bacteria.

Microbial resistance to antibiotics is an ancient and dynamic issue that has brought a situation reminiscent of the pre-antibiotic era to the limelight. Currently, antibiotic resistance and the associated infections are widespread and pose significant global health and economic burden. Thus, the misuse of antibiotics, which has increased resistance, has necessitated the search for alternative therapeutic agents for combating resistant pathogens. Antimicrobial peptides (AMPs) hold promise as a viable therapeutic approach against drug-resistant pathogens. AMPs are oligopeptides with low molecular weight. They have broad-spectrum antimicrobial activities against pathogenic microorganisms. AMPs are nonspecific and target components of microbes that facilitate immune response by acting as the first-line defense mechanisms against invading pathogenic microbes. The diversity and potency of AMPs make them good candidates for alternative use. They could be used alone or in combination with several other biomaterials for improved therapeutic activity. They can also be employed in vaccine production targeting drug-resistant pathogens. This review covers the opportunities and advances in AMP discovery and development targeting antimicrobial resistance (AMR) bacteria. Briefly, it presents an overview of the global burden of the antimicrobial resistance crisis, portraying the global magnitude, challenges, and consequences. After that, it critically and comprehensively evaluates the potential roles of AMPs in addressing the AMR crisis, highlighting the major potentials and prospects.

Genome plasticity in Candida albicans: A cutting-edge strategy for evolution, adaptation, and survival.

Candida albicans is the most implicated fungal species that grows as a commensal or opportunistic pathogen in the human host. It is associated with many life-threatening infections, especially in immunocompromised persons. The genome of Candida albicans is very flexible and can withstand a wide assortment of variations in a continuously changing environment. Thus, genome plasticity is central to its adaptation and has long been of considerable interest. C. albicans has a diploid heterozygous genome that is highly dynamic and can display variation from small to large scale chromosomal rearrangement and aneuploidy, which have implications in drug resistance, virulence, and pathogenicity. This review presents an up-to-date overview of recent genomic studies involving C. albicans. It discusses the accumulating evidence that shows how mitotic recombination events, ploidy dynamics, aneuploidy, and loss of heterozygosity (LOH) influence evolution, adaptation, and survival in C. albicans. Understanding the factors that affect the genome is crucial for a proper understanding of species and rapid development and adjustment of therapeutic strategies to mitigate their spread.

Epidemiology of Cryptococcus and cryptococcosis in Western Africa.

Cryptococcosis is a serious and sometimes fatal fungal disease caused by Cryptococcus species. Worldwide, it is estimated to kill over 180 000 annually, with 75% of deaths occurring in sub-Saharan Africa. Though cryptococcal infections are rare in otherwise healthy individuals, there have been reported cases in immunocompetent persons. Most cases occur in individuals who have weakened immune systems, particularly those with advanced HIV/AIDS, thus making West Africa a potential hotspot of the disease. Despite this, there is no recent review article with a focus on published findings on cryptococcosis in Western Africa. Common clinical symptoms include chest pain, dry cough, headache, nausea, confusion, fever, fatigue and stiffness of the neck/neurological impairment. The CNS and the lung remain its preferred target even though rare cases of attack on other parts of the body were reported in this review. Cryptococcal antigen screening and India ink preparation were the most commonly used diagnostic methods. Repeated isolation from environmental samples was observed. Overall, data on the clinical prevalence of Cryptococcus are scarce and variable in the region. The environmental prevalence ranges from 2.3% to 22%. This review covers all published research findings on cryptococcosis in West Africa till date. The epidemiological data will likely be of interest to clinicians within and outside the continent. The nations covered in this review include the following: Benin Republic, Burkina Faso, Cote d'ivoire, Ghana, Guinea, Guinea- Bissau, Mali, Nigeria, Senegal and Sierra Leone. More studies are warranted to fill the observed gaps on the epidemiology of Cryptococcus in the region.

The use of nanoparticles as alternative therapeutic agents against Candida infections: an up-to-date overview and future perspectives.

Candida spp. are opportunistic fungi that can cause severe infections especially in immunocompromised patients. Candidiasis is currently the most frequent fungal disease affecting humans globally. This rise is attributed to the vast increase in resistance to antifungal agents. In recent years, the epidemiological and clinical relevance of fungal infections caused by Candida species have attracted a lot of interest with increasing reports of intrinsic and acquired resistance among Candida species. Thus, the formulation of novel, and efficient therapy for Candida infection persists as a critical challenge in modern medicine. The use of nanoparticle as a potential biomaterial to achieve this feat has gained global attention. Nanoparticles have shown promising antifungal activity, and thus, could be seen as the next generation antifungal agents. This review concisely discussed Candida infection with emphasis on anti-candida resistance mechanisms and the use of nanoparticles as potential therapeutic agents against Candida species. Moreover, the mechanisms of activity of nanoparticles against Candida species, recent findings on the anti-candida potentials of nanoparticles and future perspectives are also presented.

Mechanism of Candida pathogenesis: revisiting the vital drivers.

Candida is the most implicated fungal pathogen in the clinical setting. Several factors play important roles in the pathogenesis of Candida spp. Multiple transcriptional circuits, morphological and phenotypic switching, biofilm formation, tissue damaging extracellular hydrolytic enzymes, metabolic flexibility, genome plasticity, adaptation to environmental pH fluctuation, robust nutrient acquisition system, adherence and invasions (mediated by adhesins and invasins), heat shock proteins (HSPs), cytolytic proteins, escape from phagocytosis, evasion from host immune system, synergistic coaggregation with resident microbiota, resistance to antifungal agents, and the ability to efficiently respond to multiple stresses are some of the major pathogenic determinants of Candida species. The existence of multiple connections, in addition to the interactions and associations among all of these factors, are distinctive features that play important roles in the establishment of Candida infections. This review describes all the underlying factors and mechanisms involved in Candida pathogenesis by evaluating pathogenic determinants of Candida species. It reinforces the already available pool of data on the pathogenesis of Candida species by providing a clear and simplified understanding of the most important factors implicated in the pathogenesis of Candida species. The Candida pathogenesis network, an illustration linking all the major determinants of Candida pathogenesis, is also presented. Taken together, they will further improve our current understanding of how these factors modulate virulence and consequent infection(s). Development of new antifungal drugs and better therapeutic approaches to candidiasis can be achieved in the near future with continuing progress in the understanding of the mechanisms of Candida pathogenesis.

Nutrition, malnutrition, and leishmaniasis.

Leishmaniasis is a vector-borne infectious disease with a long history of infecting humans and other animals. It is a known emerging or resurging disease. The host nutritional state has an indispensable role in defense against pathogens. The host defense system disorganization as a result of undernutrition is responsible for asymptomatic infections and even severe diseases. Host susceptibility and pathophysiologic severity to infection can be aggravated owing to undernourishment in a number of pathways, and infection also may aggravate preexisting poor nutrition or further increase host susceptibility. This study suggests that there may be some relationship between malnutrition and the endemicity of the parasite. The susceptibility to and severity of leishmanial infection can be altered by the body weight and serum levels of micronutrients. Nutrition not only affects the vulnerability of the host but also may affect the desire of sandfly to bite a specific host. Apart from host defense mechanism, nutritional stress also greatly influences vector competence and host-seeking behavior, especially during larvae development. The host and sandfly vector nutritional states could also influence the evolution of the parasite. It is essential to elucidate the roles that diets and nutrition play in the leishmanial life cycle. The aim of this article is to review the influences of nutrition and diets on the host susceptibility and severity of infection, preemptive and therapeutic strategy feedback, parasite evolution, and vector competence.

Comparative analysis of urinary schistosomiasis among primary school children and rural farmers in Obollo-Eke, Enugu State, Nigeria: implications for control.

OBJECTIVE: To determine the prevalence, sex-age related intensity of urinary schistosomiasis and to compare such parameters among rural school children and rural farmers in selected communities in Obollo-Eke located in Southeast, Nigeria. METHODS: A cross-sectional survey involving 1 337 school children and farmers was conducted in Obollo-Eke community between September 2006 and July 2007. Demographic data of subjects was collected using a questionnaire prepared for this purpose. Urine samples were collected and examined for haematuria and ova of Schistosoma haematobium (S. haematobium) using Medi-test Combi 9 and sedimentation technique respectively. RESULTS: The prevalence of urinary schistosomiasis based on microscopic examination of the urine sediment for the ova of S. haematobium was 17.5% while the prevalence of haematuria was 15.6%. Infection intensity varied from light to heavy. In general, the prevalence was higher among males (20.8%) than females (14.6%; P>0.05) and was slightly higher among primary school children (18.0%; n=762) than farmers (16.9%; n=575; P>0.05). The age-specific prevalence of schistosomiasis among the study subjects ranged from 8.3% to 21.2% in 0-5 years and 11-15 years age groups respectively. CONCLUSIONS: Haematuria and mean egg/10 mL urine (r = 0.95; P<0.01) showed that both procedures are reliable for the diagnosis of the disease and can be used to ascertain the prevalence of the disease in any community. The comparative analysis of urinary bilharziasis among primary school children and rural farmers demonstrated that the infection is moderately high in these two risk population groups at Obollo-Eke. A robust intervention strategy is clearly needed.

Oral Candida isolates among HIV-infected subjects in Nigeria.

BACKGROUND: Nigeria is a West African country of more than 150 million persons with the second highest case of HIV/AIDS infected patients in the world. The species spectrum of oral yeast colonization and the susceptibility to a wide range of antifungal agents is poorly understood in Nigeria especially in the south east, south south, and the northern axis. This study evaluates the species spectrum of oral colonization by Candida species in HIV-infected patients in Nigeria and the in vitro susceptibility pattern of the Candida isolates to a broad range of antifungal agents. METHODS: Two hundred oropharyngeal swabs from HIV-infected patients and 100 age-matched healthy controls were screened for yeast isolates using standard procedures and confirmed by the analytical profile index 20C along with other biochemical tests. In vitro susceptibility testing of the yeast isolates to antifungals were performed using the broth microdilution method protocol recommended by the Clinical Laboratory Scientific Institute. RESULTS: Of 200 patients screened, 120 (60%) were colonized by yeasts. C albicans was the dominating species in both groups with 54 (45%) isolated from HIV subjects. The non-albicans Candida species accounted for 55% with C tropicalis 22 (18.3%) showing the highest frequency. We observed that 11.7% of all yeasts isolates were resistant to fluconazole, 8.3% to flucytosine, 7.5% to itraconazole, and 1.7% to voriconazole. All isolates were susceptible to amphotericin B and most of them demonstrated very low voriconazole minimal inhibitory concentrations. Apart from C albicans, C tropicalis and C parapsilosis isolates were also recovered from apparently healthy control subjects. CONCLUSION: Although C albicans continues to be the dominant Candida species in oral Candida carriage of HIV-infected patients in Nigeria, the nonalbicans Candida species are increasing. Furthermore, the finding of resistant isolates in our study emphasizes the need for antifungal susceptibility testing whenever antifungal treatment is desired especially in HIV-infected subjects.

Dermatophytosis among children of Fulani/Hausa herdsmen living in southeastern Nigeria.

BACKGROUND: Dermatophytic infections are a worldwide public health problem. In Nigeria, children of nomadic herdsmen are thought to be more at risk because of their early and continuous exposure to different kinds of animals. However, little is known about the level of infection in these children in southeastern Nigeria or elsewhere within the West African sub-region. OBJECTIVE: This study investigated dermatophytic infections among children of nomadic herdsmen living in isolated camps in southeastern Nigeria from October 2008 to May 2009. METHODS: 390 children aged between 4 and 17 years with clinically suggestive lesions were sampled. Isolates were identified by microscopy, culture or both. Biochemical tests and sequencing of the ITS2 region of the ribosomal DNA were used to identify isolates with atypical morphology. RESULTS: 162 children were confirmed to be infected. Ten different species of dermatophytes were recovered with Trichophyton mentagrophytes showing the highest incidence. There was a significant difference (P < 0.05) in the frequency of isolates recovered among the different age groups screened. No significant (P > 0.05) observations were found according to gender or location of the two camps investigated. CONCLUSION: This study suggests that tinea capitis is the predominant clinical type of dermatophytosis among children exposed to different kinds of animals based on parental nomadic lifestyle. It also dominated in children with mixed infections in different anatomical sites. The high prevalence of 41.25% suggests that animal to child transmission may be very common.