Showing papers in "The African Journal of Pharmacology and Therapeutics in 2012"

Antimicrobial activity of various extracts of the sea urchin Tripneustes gratilla (Echinoidea)

Abstract: The recent appearance of a growing number of bacteria resistant to conventional antibiotics has stimulated the search for novel antimicrobial agents or lead compounds from a variety of sources, including natural sources crustaceans, molluscs and echinoderms, with particular interest on their secondary metabolites with desirable antimicrobial properties (Haug et al, 2002, Casas et al, 2010). Antimicrobial activity in several species of echinoderms collected from Gulf of California, Mexico, Caribbean and Coast of Norway has been reported (Rinehart et al, 1981; Bryan et al, 1994; Haug et al, 2002). In addition, a variety of antimicrobial factors, including steroidal glycosides (Andersson et al, 1989), polyhydroxylated sterols (Iorizzi et al, 1995), naphthoquinone pigments (Service and Wardlaw, 1984), lysozymes (Canicatti and Roch, 1989; Stabili and Pagliara, 1994), complement like substances (Leonard et al, 1990) and antimicrobial peptides (Beauregard et al, 2001) have also been isolated from echinoderms. These findings suggest that marine echinoderms are a potential source of new types of antibiotics for pharmaceutical development. Tripneustes gratilla (Echinoidea) collected from the Kenyan Coast. Unfortunately, in most of these studies on antimicrobial activity in echinoderms, whole bodies or body walls have been tested for activity. Recently, Haug et al. (2002) observed wide differences in antibacterial activities between different extracts and organs/tissues, as well as between species, of three echinoderms. Whether the same antibacterial factors are responsible for the activity in all organs or tissues remains unclear. The present work focused on screening and comparing antimicrobial and hemolytic activities in different organs/tissues of the sea urchin

Antimicrobial activity of organic total extracts of three Kenyan medicinal plants

Abstract: In recent years, drug resistance to human pathogenic bacteria and fungi has increasingly been reported all over the world (Levy and Marshall, 2004; WHO 2004). Consequently, the increasing prevalence of multidrugresistant strains of microorganisms raises an urgent need to search for new sources of antimicrobial agents (Sieradzki et al, 1999) alongside other strategies such as regulated and rational use of antibiotics (Hernandez, 2005). The vast majority of traditionally used medicinal plants have not been adequately evaluated. This study was therefore undertaken to screen organic extracts obtained from three Kenyan medicinal plants for antibacterial and antifungal activity as a basis for further phytochemical studies. The plants to be studied were selected on the basis of ethnopharmacological reports of their use in traditional medicine; this approach is generally considered effective in the discovery of new bioactive agents from higher plants (Kloucek et al, 2005).

In vivo antimalarial and acute toxicity properties of hexane and chloroform extracts from Clausena anisata (Willd.) Benth.

Abstract: Malaria is a disease caused by Plasmodium parasites and, though preventable and curable, is still one of the greatest global public health problems especially in sub- Saharan Africa. This can be partly attributed to the malaria in endemic areas. Unfortunately, recent reports indicate a decline in efficacy of artemisinin derivatives along Thai-Cambodia border, a site historically known for the recurrent emergence of drug resistant malaria parasites (Dondorp et al, 2009; Noedl et al, 2008). New classes of antimalarial agents are therefore urgently needed given that drug resistance is likely to eventually compromise the efficacy of currently available antimalarial drugs; identification of lead antimalarial agents from medicinal plants could boost the search. Clausena anisata in vivo antimalarial activity and acute toxicity of C. anisata extracts were investigated. The plant was selected as it has been traditionally used to treat malaria (Kokwaro, 2009; Beentje, 1994). (Willd.) Benth is a deciduous shrub/tree whose leaves are aromatic. In Kenya, it is known locally as Mjarikali (Swahili) and Mutathi (Kikuyu). Traditionally, soup boiled with the roots of the plant was given to women after birth to cleanse the uterus. This soup is also highly recommended for headache, malaria, influenza and indigestion. Twigs are used as toothbrushes and are believed to cure toothache. Decoctions of the root are also drunk to treat syphilis (Kokwaro, 2009; Beentje, 1994; Gachathi, 1989). Pharmacological activities associated with extracts from this plant include antifungal and antibacterial activity (Senthilkumar and Venkatesalu, 2009; Hamza et al, 2006; Gundidza et al, 1994), antidiabetic activity (Ojewole, 2002), anticonvulsant activity (Makanju, 1983) angiotensin converting enzyme (ACE) inhibitory activity (Duncan et al, 1999) and antiviral activity (Ayisi and Nyadedzor, 2003). Phytochemical investigations indicate carbazole alkaloids as the major component of this plant (Ito et al, 2000; Ito et al, 2009). Coumarins and limonoids have also been isolated (Ngadjui et al, 1991; Ngadjui et al, 1989; Lakshmia et al, 1984). Pharmacological activities associated with carbazole alkaloids include antifungal, antibacterial and antiviral activities (Ito et al, 2009; Ito et al, 2000; Chakraborty et al, 1995). Coumarins are reported to have anticoagulant properties (Emerole et al, 1981). Steam distillation of fresh leaves yielded sweet smelling, brownish-yellow oil whose major component is the acute toxin estragole (Okunade, 1987). As part of our continuing efforts to identify antimalarial agents from medicinal plants, in vivo antimalarial activity and acute toxicity of C. anisata extracts were investigated. The plant was selected as it has been traditionally used to treat malaria (Kokwaro, 2009; Beentje, 1994).

Glucose-lowering effects of Momordica charantia (Karela) extract in diabetic rats

Abstract: Background: Momordica charantia (MC) is a plant commonly used for both its nutritional and glucose-lowering effects. It has however not been fully validated in diabetes management due to insufficient empirical evidence. The current study thus investigated its effects on blood glucose levels in diabetic rats. Method: Fourteen six-month old, alloxan-induced diabetic Sprague Dawley rats weighing between 200 – 250 g were assigned to two equal groups (control and experimental). Momordica charantia juice extract was administered (10ml/kg) to the experimental group for 28 consecutive days. An equal dose of normal saline was administered to the controls. Fasting blood glucose (FBG) levels were assessed once weekly for 4 consecutive weeks. Thereafter, intraperitoneal glucose tolerance test (IPGTT) was performed. Results: The experimental group achieved normal glucose levels within 14 days of MC administration. At day 28, FBG levels were significantly lower in the experimental group compared to the control (3.27±0.20 vs. 7.59±1.26 mmol/l, p=0.01). In IPGTT, FBG levels were significantly lower in the experimental group compared to the control through the 180 minute period of observation. Conclusion: Momordica charantia has a glucose-lowering effect in diabetic rats within 14 days of administration. It also prevents fluctuations in FBG levels, and thus has potential therapeutic use in diabetes management.

Antioxidant, acetylcholinesterase inhibitory activity and cytotoxicity assessment of the crude extracts of Boophane disticha

Abstract: 1. Introduction Alzheimer’s disease (AD) is the most common neurodegenerative disease and is characterized by memory impairment, cognitive dysfunction, behavioral disturbances and deficits in daily living (Konrath et al, 2012). Approaches to enhance cholinergic function in AD have included stimulation of cholinergic receptors or prolonging the availability of acetylcholine (ACh) released into the neuronal synaptic cleft by inhibiting ACh hydrolysis through the use of acetylcholinesterase (AChE) inhibitors (Howes and Houghton, 2003). Tacrine was the first widely used AChE inhibitor (Summers, 2006). Second generation AChE inhibitors with longer half-lives than tacrine, such as donepezil, galanthamine and rivastigmine, have since been developed and are currently in use (Shah et al, 2008). In addition, several lines of evidence indicate that reactive oxygen species are associated with the pathogenesis of AD, as some cellular characteristics of this disease are either causes or effects of oxidative stress (Zhu et al, 2004; Sultana et al, 2006; Konrath et al, 2012). Generally, the physiological role of antioxidant compounds is to attenuate the oxidation chain reactions by removing free-radical intermediates (Liu and Nair, 2010). Since a large amount of evidence demonstrates that oxidative stress is intimately involved in age-related neurodegenerative diseases, there have been a number of studies which have examined the positive effects of antioxidants in reducing or blocking neuronal death occurring in the pathophysiology of these disorders (Ramassamy, 2006). Consequently, the use of antioxidants has been explored in an attempt to slow AD progression and neuronal degeneration (Howes and Houghton, 2003). Toxicity testing is an essential requirement for the development of modern pharmaceutical compounds. Medicinal plants are assumed to have low toxicity due to their long-term consumption by humans and animals (Luseba et al, 2007; Verschaeve and van Staden, 2008; Aremu et al, 2011). However, several studies have shown that many plants used as food or medicine, have potential toxic effects (Du Plooy et al, 2001; Barlow and Schlatter, 2010). Almost all known AChE inhibitors have several drawbacks, such as hepatotoxicity, short duration of biological action, low bioavailability, adverse cholinergic side effects in the periphery and narrow therapeutic windows (Lee et al, 2011). Some common synthetic antioxidants including butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) have been reported to be toxic (Aremu et al, 2011). Therefore, the search for new AChE inhibitors and antioxidants, particularly from natural products, with low toxicity and higher efficacy continues. Many plants are reputed to have ‘anti-ageing’ or ‘memory-enhancing’ effects and are used traditionally to treat several neurodegenerative diseases (Howes and Houghton, 2003). One such plant, Boophane disticha (L.f.) Herb. belongs to the family Amaryllidaceae. It is an attractive, deciduous bulbous plant with a thick covering of dry scales above the ground and is widely distributed in Africa, ranging from Sudan in the north to the Western Cape Province in the south (Wrinkle, 1984). Decoctions of bulb scales are given to sedate violent, psychotic patients while bulb infusions are reported to be used to treat mental illness (van Wyk and Gericke, 2000; Sobiecki, 2002). Bulb decoctions are also used in the treatment of headaches, abdominal pain, weakness, sharp chest pains and persistent bladder pains, as well as treatment of varicose ulcers, relief of urticaria, and cancer (Botha et al, 2005). This study was aimed at evaluating the AChE inhibitory and antioxidant activity of the bulbs and roots of B. disticha to partially justify its traditional use in treatment of neurodegenerative diseases. The safety of using this plant in traditional medicine was also investigated by assessing its toxicity using the MTT and neutral red assays.

Larvicidal effect of Mundulea sericea (Leguminosaea) plant extract against Aedes aegypti (L.) (Diptera: Culicidae)

Abstract: Introduction The medical importance of mosquitoes as vectors for the transmission of serious diseases that cause morbidity, mortality, economic loss, and social disruption such as malaria, lymphatic filariasis, and viral diseases is well recorded (Becker et al, 2003). Aedes aegypti, the main carrier for viruses that cause dengue and dengue hemorrhagic and yellow fevers, is found majorly in the tropics and subtropics. There is no effective vaccine against dengue, and thus the only way of significantly lowering the incidence of this disease is through mosquito control (Malavige et al, 2004). Chemical measures were first tried, but they failed since their overuse led to disruption of natural biological control systems and outbreak of new insect species. In addition, use of insecticides led to the development of mosquito resistance, environmental pollution, and undesirable effect on non-target organisms (Brown, 1986). In a bid to resolve these problems, interest in insecticides of natural origin, specifically plant-derived products has recently received close attention. Several studies have emphasized the importance of research and development of herbal substances for controlling mosquitoes (Shaala et al, 2005). Their results may vary, but natural plant products may be a possible alternative to synthetic substances, as they are effective and compatible with human and animal life and the environment (Chaithong et al, 2006). The genus Mundulea consists of about 15 species, widespread throughout Africa, Madagascar, Mauritius, India, Sri Lanka and Papua New Guinea. Only a single species, Mundulea sericea, is found in Southern Africa. This species occurs in South Africa, Botswana, Namibia and Angola, north to tropical Africa, and east to Madagascar, India, Sri Lanka and Papua New Guinea (Watt and Breyer-Brandwick, 1962). Mundulea sericea is one of the commonest fish poisons where both bark and seeds are used (Neuwinger, 2004). In addition, the Chinese used M. sericea to control tobacco budworm Heliothis virescens (Lepidopteriae: Noctuidae) (Yoshida and Toscano, 1994). The toxic principal of the plant is rotenone, an isoflavonoid (Vedcourt and Trump, 1969). The rotenoids deguelin and tephrosin are the potent active principles which have been isolated from extracts of M. sericea (Luyengi et al, 1994). Deguelin is a natural plantderived rotenoid, most commonly used as an insecticide in Africa and South America (Udeani et al, 1997). Rotenoids from the bark of M. sericea have been commercially used as insecticide. These chemical compounds in the bark, leaves and seed are the active compounds responsible for the fish poison. It is reported that the strength varies geographically (Watt and Breyer-Brandwick, 1962). The current study involved extraction and evaluation of root bark and seedpod of M. sericea for larvicidal activities on Aedes aegypt.

Peculiar glycemic patterns in alloxaninduced diabetes animal model

Abstract: Animals are commonly used for experimentation in academic and research institutions (Kimwele et al, 2011). The reliability of a study is partly determined by the animal model used. The researcher must therefore have a fine understanding of animal models when designing animal studies. The current study focuses on animal models used in investigating diabetes mellitus (DM), and its management. These animal models differ significantly and no single one has been reported to accurately represent the essential pattern of type 2 DM in humans, in whom the disease is often preceded by obesity and various molecular changes. Animal models are developed by techniques such as pancreatectomy, chemical induction, genetic engineering, molecular biology and islet cell transplantation (Junod et al, 1969; conducted in animal models, notably dogs and rodents (Lanza et al, 1999). In the majority of studies, chemical-induced diabetes models have been utilized (Frode and Medeiros, 2008). Such chemicals include alloxan (Lenzen, 2008), and streptozotocin (Junod et al, 1969). As at 2010, streptozotocin had reportedly been used in 69% of chemical-induced diabetes animal models, whereas alloxan was the second most commonly used chemical at 31% (Etuk, 2010). Alloxan is a urea derivative which causes selective necrosis of the pancreatic islet β-cells (Etuk, 2010). It is used experimentally to induce type 2 DM in animals such as rabbits, rats, mice and dogs. The experimental dose of the drug needs careful consideration in order to avoid excessive pancreatic tissue damage. The most frequently used intravenous dose of alloxan in rats is 65 mg/kg, but its effective dose must be higher when it is administered intraperitoneally or subcutaneously (Antia et al, 2005). With the rising use of alloxaninduced DM models, different dosages and different methods of inducing diabetes have been reported. Though most methods have demonstrated success, a handful have reported failed induction or variation in blood glucose following alloxan administration (Etuk, 2010). The current study was thus carried out to assess the pattern of blood glucose following intraperitoneal administration of alloxan (125 mg/kg).

The quality of PMTCT services and uptake of ARV prophylaxis amongst HIV positive pregnant women in Kakamega district, Kenya

Abstract: Background: The success of a PMTCT programme depends on the quality of services offered at health facilities. Indicators of quality include the competence and attitude of the counsellor and uptake of ARV prophylaxis. Objective: This study looked at the relationship between quality of prevention of mother to child transmission of HIV (PMTCT) services and the maternal ARV prophylaxis uptake in Kakamega district, Kenya. Methods: The study was a cross-sectional study. Thirty health facilities and health care workers were sampled using multistage sampling. From these health facilities, 119 HIV positive pregnant women were sampled by convenience s ampling. The PMTCT counsellors and HIV positive pregnant were interviewed using a structured questionnaire. Statistical analysis: Descriptive data analysis was carried out on all variables. Categorical variables across groups were compared using the Fisher Exact test. Logistic regression was used to identify determinants of uptake of ARV prophylaxis at facility level Results: About 86.7% of the health facilities sampled had satisfactory quality of PMTCT services and 89% of HIV positive pregnant women reported that they received satisfactory PMTCT counselling services. About 90% of the counsellors have received PMTCT training and the mean score in a knowledge test was 77.2%. However, providers generally had a negative attitude towards their clients. On regression analysis, there was no significant association between various aspects of quality and infant ARV prophylaxis uptake. Uptake at facility level was determined by the district and type of health facility. Conclusion : The quality of service in the sampled facilities was generally good but this did not influence the level of uptake of maternal or infant ARV prophylaxis. Key words: Prevention of Mother to Child Transmission (PMTCT), ARV prophylaxis, HIV-positive pregnant women.

Were the WHO-recommended Human Influenza Vaccine Formulations Appropriate for Kenya During the 2010-2011 Season? Inferences from the HA1 Gene Analysis

Abstract: Phylogenetic analyses revealed that influenza B viruses were closely related to B/Brisbane/60/2008 vaccine strain while A (H1N1) pdm09 viruses were genetic variants of A/California/07/2009. The Kenyan A (H1N1) pdm09 isolates had P83S, D97N, S185T, I321V and E374K amino acid substitutions. Influenza A/H3N2 isolates showed K62E, T212A and S214I simultaneous amino acid substitutions when compared to A/Perth/10/2009. The K62E change occurred at antigenic site E. Majority of the Kenyan H3N2 isolates further had S45N and K144N amino acid substitutions at sites C and A respectively, which introduced N-glycosylation motifs absent in the vaccine strain.

Lumefantrine-resistant and Piperaquine-resistant Plasmodium berghei show cross-resistance to Primaquine but not to Atovaquone

Abstract: Background: Malaria affects 300-500 million people annually and kills more than 1 million, with majority of the clinical cases and deaths occurring in Sub-Saharan Africa. Rapid development of drug resistance remains a major challenge in malaria control and has lead to use of combined antimalarial therapies. Resistance to an antimalarial drug may however, be selected for by another drug in which the mechanism of resistance is similar. Objective: This study sought to establish cross-resistance patterns between four antimalarials namely atovaquone (ATQ), primaquine (PMQ), lumefantrine (LM) and piperaquine (PQ) using murine malaria models. Method : The activities of ATQ and PMQ against drug sensitive, PQ and LM-resistant Plasmodium berghei lines was assessed using the 4-day test and 90% index of resistance (I90 ) determined. Results: Analysis of cross-resistance patterns showed a significant decrease in PMQ sensitivity (I 90 of 6.39), and a slight but not significant decrease in ATQ (I 90 of 1.19) activity towards the LM-resistant P.berghei ANKA. Conclusion : PQ-resistance in P. berghei is associated with a significant resistance of PMQ (I 90 of 12.22) and a slight, though not significant reduction in ATQ (I90 of 1.27) efficacy.

Screening of Indigofera lupatana Baker F. root extracts for antibacterial activities

Abstract: Herbal remedies as cheap alternatives to conventional medicine have contributed significantly to rural livelihoods. Apart from the traditional healers practicing herbal medicine, many people are involved in collecting and trading medicinal plants. The World Health Organization (WHO) estimates that 80% of the world’s population depends on medicinal plants for their primary health care (Mothana et al, 2008; Ngoci et al, 2011). The use of traditional medicine has been explored globally and is widely used in developing countries as an alternative or to complement conventional medicine (Rates, 2001; Gupta et al, 2010). Natural products, either as pure compounds or as standardized plant extracts, provide exceptional opportunities for new drug leads because of the unmatched chemical diversity of naturally derived compounds (Cowan, 1999; Parekh and Chanda, 2007; Mariita et al, 2010; Ngoci et al, 2011). Scientific interest in medicinal plants has burgeoned due to the recognized efficacy of plant derived drugs and everpresent concerns about the side effects of modern medicinal substances. This has fuelled the intensive investigation of new molecular structures from the plant kingdom as potential medicinal compounds (Mariita et al, 2010). As a result, drugs derived from unmodified natural products or semi-synthetic drugs obtained from natural sources accounted for 78% of the new drugs approved by the United States Food and Drug Administration (FDA) between 1983 and 1994 (Suffredini et al, 2006; Ngoci et al, 2011). This underscores the importance of screening natural products. Infectious diseases are a leading cause of human and animal mortality. This is further aggravated by the rapid development of multi-drug resistance to available antimicrobial agents (Doughart and Okafor, 2007; Ngoci et al, 2011), their limited anti-microbial spectrum, their side effects (Huie, 2002), and emergence and reemergence of opportunistic infections. Therefore, studies aimed at identifying and characterizing of the substances that exhibit activity against infectious microorganisms, yet showing no cross resistance with existing antibiotics, are required (Olila et al, 2001). In recent years, pharmaceutical companies have focused on developing drugs from natural products that promises to counter the limitations of conventional antibiotics (Doughart and Okafor, 2007). The bio-activity of natural products is due to phytochemicals, a group of secondary metabolites often elaborated for the plant defense against pests and herbivores or to gain an advantage over competing agents. These phytochemicals inadvertently also protect humans against pathogens (Ngoci et al, 2011). Some phytochemicals are known to have antimicrobial properties, immune-modulative properties, provide nutrition for normal cell health and repairs, inhibit carcinogens and act as antioxidants. Indigofera lupatana Baker F., locally called ‘mugiti’ by the Mbeere community in Kenya, is a woody shrub found in Acacia-Combretum ecological zones of Mbeere. It is widely used for its perceived medicinal value in treating coughs and diarrhea (Riley and Brokensha, 1988; Ngoci et al, 2011), gonorrhea and pleurisy (Kokwaro, 1993; Ngoci et al, 2011). There is apparently no documented scientific report on anti-microbial properties of this plant. This lack of scientific corroboration has often constituted a major constraint to the consideration of the use of herbal remedies in conjunction with or as an affordable alternative to conventional medical treatment (Okeke et al, 2001). Knowledge of the chemical constituents of plants is desirable not only for the discovery of therapeutic agents, but also because such information may be important in identifying new sources of substances of economic value such as tannins, oils, gums, and precursors for the synthesis of complex chemical substances. In addition, the knowledge of the chemical constituents of plants would further be valuable in discovering the actual value of folkloric remedies (Mojab et al, 2003). This study was therefore undertaken to determine the antibacterial properties of hexane, ethyl acetate and dichloromethane root extracts of I. lupatana Baker F.

The Impact of Human Immunodeficiency Virus and Human Papillomavirus Co-Infection on HPV Genotype Distribution and Cervical Lesion Grade in a Semi-Urban Population in Tigoni, Kenya

Abstract: Conclusion: HIV infection was a significant risk factor in HPV infection with 65.5% of cases being both HPV and HIV infected. Over 77% of those individuals who had a CIN III or greater were HPV positive. HR-HPV types were found across all diagnostic categories in the cases that had a cervical tissue biopsy with HPV type 16 being the most dominant type, particularly in high grade lesions.

Dose-dependent myocardial toxicity of Mangifera indica during diarrhoea treatment

Abstract: The use of herbal medicine is on the rise worldwide (Trindle et al, 2005). Many cultures have beliefs and prejudices towards the treatment of various morbidities that often affect their attitudes towards conventional medical practices. It would therefore be expedient to supplement, rather than to supplant such beliefs and cultural customs. This is the basis of ethnopharmacology, a science that aims to validate (or invalidate) the use of such plants for their alleged beneficial properties. The easy availability, low cost and belief of fewer associated side effects are the major attractions to herbal medicine among such communities. One such traditional practice is the use of mango (

Uganda Arboviruses Surveillance Activities

Abstract: Background: Arboviruses research in Uganda dates before the 1930s. More than 38 arboviruses and over 224 mosquito species together with many other insect vectors are documented to occur in Uganda. However, arboviruses research activities came to a virtual standstill in the 1980s. Surveillance for arboviruses was reinstated in 2007 through the Uganda Arbovirus Program 2007 to collect new information on arbovruses in Uganda.

Seroprevalence of Chikungunya, West Nile Virus and Dengue Virus in Febrile Patients visiting selected health facilities in Trans Nzoia County

Abstract: Methods: We collected 1578 serum samples collected from febrile adults with no evidence of malaria or typhoid exposure visiting Andersen Medical Clinic, Endebess Sub District Hospital and Kitale District Hospital. We used indirect ELISAs to screen for exposure to Dengue, Chikungunya and West Nile Viruses, and Plaque Reduction Neutralisation Tests to confirm the status of those samples that were ELISA positive.

Potential Animal Sources of Antibodies for the Development of a Chloramphenicol Enzyme-Linked Immunosorbent Assay

Abstract: The use of chloramphenicol (CAP) in veterinary medicine in the European Union (EU) is currently limited to pets and non-food-producing animals (European Decision 2003/181/EC). It was banned in 1994 from use in any food-producing animals in the EU and also in other developing countries including Kenya. This was due to the fact that it causes bone-marrow depression leading non-dose related aplastic anaemia in human. A minimum required performance limit (MRPL) of 0.3 μg/kg has been established. A typical testing scheme for the presence of the antibiotics in samples from food producing animals employs a rapid and low cost screening assay followed by confirmatory analysis using an analytical chemical method. CAP-ELISA was African Journal of Pharmacology and Therapeutics Vol. 1 No. 2 Pages 41-45, 2012

A spatially-explicit simulation model of Rift Valley fever transmission

Abstract: Methodology: The model involves two hosts (cattle and sheep) and two vectors (Aedes spp. and Culex spp.). Host dynamics are simulated using an individual-based model while vectors dynamics are simulated using compartmental model. Hosts’ characteristics and how they utilize their environment are programmed using static and dynamic rules. These are implemented in C++ programming language. The landscape on which the simulated processes take place is subdivided into spatial lattices of 500 x 500 m using a grid.

Evidence in Kenya of Reassortment Between of Reassortment BetweenSeasonal Influenza A(H3N2) and Influenza A(H1N1)pdm09 to yield A(H3N2) Variants With the Matrix Gene Segment of A(H1N1)pdm09

Abstract: Influenza vaccines and antiviral drugs are the mainstay for preventing influenza and reducing the impact of influenza epidemics. Currently, there are two classes of antiviral drugs available for preventing and treating the M gene. The neuraminidase inhibitors (NAI’s) interrupt the replication cycle by preventing virus release and allowing progeny virus to clump (Monto et al, 2002). The rapid emergence of adamantine drug resistant influenza A virus strains has limited these drugs’ clinical effectiveness. The origin and evolution of antiviral drug resistance amongst influenza viruses can occur through different molecular mechanisms that also drive the evolution of the virus. The most crucial of these mechanisms result from the segmented nature of its genome. This permits the formation of new progeny viruses with novel combinations of segments through reassortment when two or more different virus subtypes infect a single cell, a phenomenon referred to as antigenic shift. This process is capable of introducing new genes in circulating viral populations that can drastically change the biological properties of the virus. Studies have shown that reassortment led to an increase in the frequency of amantadine-resistant seasonal influenza A(H1N1) viruses since the 2005-2006 season (Yang et al, 2011). This underscores the necessity to monitor genome dynamics in circulating influenza viruses because it is through such molecular surveillance that we are able to understand the evolution and mechanisms of the emergence and spread of antiviral resistance among influenza A viruses (Boni et al, 2010). Thus, we set out to qualitatively analyze human influenza A(H3N2) viruses that circulated in Kenya in 2010, the period when influenza A(H3N2) and A(H1N1)pdm09 [previously referred to as swine flu] (WHO, 2011a) begun to co-circulate in the human population in the country, determine evidence of reassortment amongst the co-circulating subtypes and relate any such events to influenza antiviral resistance in the country. We applied the current laboratory testing protocol which involves routinely sequencing the HA, M and NA gene segments of the influenza viruses. These three gene segments were selected because they are the main antigens (NA & HA) and drug targets (M & NA) of the influenza A virus. Herein we provide evidence that indeed there was reassortment involving at least the M gene segment amongst cocirculating influenza A viruses in Kenya during this period.

Amino Acid changes at the hemagglutinin antigenic site amongst Kenyan influenza A(H1N1)pdm09 viruses in 2009-2010

Abstract: Methodology: Nasopharyngeal samples from patients meeting the WHO pandemic influenza case definition were collected from consenting patients between 2009 and 2010 from across Kenya. The detection of influenza A(H1N1)pdm09 viruses was carried out using real-time RT-PCR. The positive samples were then cultured in MDCK cells and confirmed using the HAI assay. 23 isolates from this period were selected for RNA extraction followed by PCR amplification of the HA1 gene segments. Nucleotide sequencing was performed using the Sanger method followed by data analysis using a suite of bioinformatics tools.

Factors associated with mother to child transmission of Human Immunodeficiency Virus in Kenya

Abstract: Results: A total of 32,671 infant samples were tested between January 2010 and March 2012. 29,571 (91.5%) infants were HIV negative and 2,666 (8.3%) were HIV positive. The odds of being seropositive were higher in females (OR 1.15, p=0.0010) overall, and were also higher than for males in most age categories. The odds of positivity associated with exclusive breastfeeding before 6 months were 0.48 (p = 0.0000), exclusive replacement feeding before 6 months 0.77 (p = 0.0393), mixed feeding before 6 months 1.88 (p= 0.0000), breastfeeding after 6 months 2.14 (p= 0.0000), and not breastfeeding after 6 months 1.66 (p= 0.0000). The odds of seropositivity were 2.54 (p=0.0000) in the absence of maternal prophylaxis and 2.96 (p= 0.0000) without infant prophylaxis. All other prophylactic approaches were associated with lower odds of seropositivity. Babies who received no prophylaxis and breastfed beyond six months, whose mothers received no prophylaxis, faced the highest seropositivity odds (OR 2.11, p = 0.0086).

Investigation of Prader-Willi-like Phenotype using a Whole Genome Array

Abstract: Introduction Prader-Willi syndrome (PWS) is characterised by obesity, short stature, small hands and feet, neonatal hypotonia with difficulty in feeding at birth, hypogonadism and eye problems. At about two years of age the feeding difficulties with poor suck are gradually replaced by hyperphagia and obsession with food, leading to the obesity. In addition to developmental delay which is manifested by short stature, small hands and feet, growth hormone deficiency and hypogenitalism/hypogonadism, there are also behavioural characteristics including learning disabilities, temper tantrums, aggression, repetitive speech, obsessive compulsive behaviour, sleep disorder and skin picking (Cassidy and Driscoll, 2009). This disparate collection of symptoms led Holm et al (1993) to define the major and minor characteristics which allowed a clinical diagnosis of this the most common genetic form of obesity. Consensus diagnostic criteria were defined and weighted scores in which the major criteria were awarded one point and the minor criteria half a point calculated. A score of 8 or more is clinically diagnostic for PWS. The majority of people with PWS have a paternally derived deletion of approximately 5-7Mb in 15q11-q13, others have maternal disomy of chromosome 15 (UPD15mat) and a minority have a defect of the imprinting centre located in exon 1 of the SNRPN gene which leads to a maternal imprint on the paternally derived chromosome. Any of these abnormalities will result in loss of the paternal contribution to the Prader- Willi syndrome critical region (PWSCR), demonstrated by loss of a paternally derived unmethylated band at the imprinting centre and a lack of expression of the SNRPN gene. Although these do not differentiate between the different genetic types of PWS they are diagnostic for the syndrome (Cassidy and Driscoll, 2009; Ramsden et al, 2010; Zeschnigk et al, 1997). Within 15q11-q13 the complex imprinted SNURF/SNRPN gene hosts several untranslated snoRNA genes located within intronic sequences. The finding of a microdeletion involving SNORD116 in a boy with PWS led to the identification of this snoRNA as the candidate gene for the syndrome (Sahoo et al, 2008). In the course of a large study of PWS in the UK (Whittington et al, 2001; Soni et al, 2007) three people were identified who fulfilled the criteria for a clinical diagnosis of the syndrome but not the genetic laboratory diagnostic criteria. The Affymetrix Cytogenetics Whole-Genome 2.7M array while providing high resolution whole genome coverage reliably detects changes in copy number. Deletions and/or duplications present in all three participants if involved in annotated genes could potentially contribute to the Prader-Willi-like phenotype. Candidate genes can subsequently be evaluated to estimate their transcription levels and compared with those shown by people with PWS and with unaffected individuals.

Risk Association between Human Leucocyte Antigens (HLA) and Cervical Neoplasia in Kenyan Women

Abstract: Cervical cancer is the second most common cause of cancer mortality among women worldwide (Franco et al, 2003). Epidemiological studies have shown a strong link between human papilloma virus (HPV) infection and the development of cervical cancer (Franco et al, carcinogenic process (Chan et al, 2005). Most HPV infections are transient and regress spontaneously and only a minority of women develops persistent infection that with time may evolve into cervical intraepithelial neoplasia and/or progress to invasive cervical cancer(Villa, 1997; Franco et al, 1999). Given that host immune response to HPV is thought to be an important determinant of HPV acquisition and progression to high-grade cervical lesions and cancer, it is plausible that human leucocyte antigen (HLA) variations may affect pathogenesis of cervical neoplasia (Beskow et al, 2005; Clerici et al, 1997; Hildesheim et al, 1997). The major histocompatibility complex is a highly polymorphic gene cluster on the short arm of chromosome six. The genes in this cluster are divided into three classes with different roles in immune responses. HLA gene polymorphisms result in variations in peptide-binding cleft, therefore influencing the antigens bound and presented to T cells (Beskow et al, 2005; Wang e al, 2005). The HLA class I genes (HLAA, -B, and –C) present foreign antigens to CD8+ Cytotoxic T lymphocytes, while class II genes (HLA-DR, - DQ and –DP) present antigenic peptides to CD4+ T helper cells and are important in host immune responses to viruses and other pathogens (Wang et al, 2001).