Drugs for the control of parasitic diseases: current status and development in schistosomiasis

The morbidity caused by schistosomiasis has been controlled in China, Egypt and the Philippines mainly by the widespread use of the safe and efficacious drug praziquantel (PZQ), and by oxamniquin and PZQ in Brazil. To date, there is no evidence of development of clinically relevant resistance. Thanks to the commitment of national governments at the World Health Assembly in 2001, and the emergence of significant funding for control, it is predicted that there will soon be more widespread use of PZQ in sub-Saharan Africa, where morbidity due to schistosomiasis is most prevalent. There are currently no available alternative drugs to PZQ (with the possible exception of oxamniquin), although perhaps PZQ analogues could be developed. Artemether, used to control malaria, is effective against immature schistosomes, but is less effective against adult worms. The efficacy of myrrh, recently marketed as an antischistosomacide in Egypt, has not been independently confirmed.     

Effect of Commiphora molmol on leukocytes proliferation in relation to histological alterations before and during healing from injury

Myrrh, Commiphora molmol has been used as anti-inflammatory and wound healing commercial product. Leukocyte count had been reliable indicator for clinicians to monitor progress of healing for their patients. We hypothesized that myrrh supplement participate in the activation of leukocyte proliferation pathway prior and post skin injury and gastric ulcer. The purpose of the present study was to examine long-term effect of myrrh on leukocytes proliferation before injury and during different stages of healing. Results showed that all types of leukocytes were significantly (p < 0.05) higher in the myrrh-treated groups before and during healing. The pretreatment with myrrh offered a time-dependent rise in leukocytes proliferation. Microscopic examination of blood smear from myrrh-treated rats with skin injury, showed an elevated count of middle-sized lymphocytes and neutrophils that were characterized with well-defined nuclear lobules and rich-granules cytoplasm. Furthermore, the microscopic examinations of the spleen and lymph nodes of myrrh-treated rats with skin injury, showed an increased thickness of lymphatic sheath around the arterioles in the white pulp that was associated with high density of the medium-sized lymphocytes in the secondary lymphoid follicles in the lymph nodes with engorged sinusoids. As myrrh enhanced leukocytes proliferation before injury, it can be concluded that myrrh posse’s antigenic-driven responses and that indicated some foreignness or toxicity of some constituents of myrrh. Because myrrh helped to maintain the relative rise of leukocytes counts throughout healing period and that implied it activated late steps of both proliferation and differentiation pathways for all types of leukocytes during effective phase of the specific immune responses.     

The epidemiological and molecular aspects of influenza H5N1 viruses at the human-animal interface in Egypt

With 119 confirmed cases between March 2006 and December 2010, Egypt ranks second among countries reporting human H5N1 influenza virus infections. In 2009–2010, Egypt reported 68 new human cases and became the new epicenter for H5N1 infections. We conducted an epidemiological and molecular analysis in order to better understand the situation in Egypt. The onset of new cases peaked annually during the winter and spring months, with majority of cases reported in the Nile Delta region. Most cases were less than 18 years old (62%) and females (60%). The overall case-fatality rate was 34% and significantly increased by age. There was a significant difference between the case-fatality rates among females and males. We observed a significant drop (p = 0.004) in case fatality rate in 2009 (10%) as compared to higher rates (36%–56%) in other years. Hospitalization within 2 or 3 days after onset of symptoms significantly decreased mortality. Molecular analysis showed that variations do occur among viruses isolated from birds as well as from humans in Egypt, and these mutations were especially noted in 2009 viruses. As the epidemiological profile of Egyptian cases differs from other countries, there is an urgent need to conduct prospective studies to enhance our understanding of incidence, prevalence, and determinants of virulence of human infections with avian H5N1 influenza viruses.     

Effect of myrrh and thyme on Trichinella spiralis enteral and parenteral phases with inducible nitric oxide expression in mice

Trichinellosis is a serious disease with no satisfactory treatment. We aimed to assess the effect of myrrh (Commiphora molmol) and, for the first time, thyme (Thymus vulgaris L.) against enteral and encysted (parenteral) phases of Trichinella spiralis in mice compared with albendazole, and detect their effect on inducible nitric oxide synthase (iNOS) expression. Oral administration of 500 mg/kg of myrrh and thyme led to adult reduction (90.9%, 79.4%), while 1,000 mg/kg led to larvae reduction (79.6%, 71.3%), respectively. Administration of 50 mg/kg of albendazole resulted in adult and larvae reduction (94.2%, 90.9%). Positive immunostaining of inflammatory cells infiltrating intestinal mucosa and submucosa of all treated groups was detected. Myrrh-treated mice showed the highest iNOS expression followed by albendazole, then thyme. On the other hand, both myrrh and thyme-treated groups showed stronger iNOS expression of inflammatory cells infiltrating and surrounding encapsulated T. spiralis larvae than albendazole treated group. In conclusion, myrrh and thyme extracts are highly effective against both phases of T. spiralis and showed strong iNOS expressions, especially myrrh which could be a promising alternative drug. This experiment provides a basis for further exploration of this plant by isolation and retesting the active principles of both extracts against different stages of T. spiralis.     

The epidemiology and iatrogenic transmission of hepatitis C virus in Egypt: a Bayesian coalescent approach

Hepatitis C virus (HCV) is a leading cause of liver cancer and cirrhosis, and Egypt has possibly the highest HCV prevalence worldwide. In this article we use a newly developed Bayesian inference framework to estimate the transmission dynamics of HCV in Egypt from sampled viral gene sequences, and to predict the public health impact of the virus. Our results indicate that the effective number of HCV infections in Egypt underwent rapid exponential growth between 1930 and 1955. The timing and speed of this spread provides quantitative genetic evidence that the Egyptian HCV epidemic was initiated and propagated by extensive antischistosomiasis injection campaigns. Although our results show that HCV transmission has since decreased, we conclude that HCV is likely to remain prevalent in Egypt for several decades. Our combined population genetic and epidemiological analysis provides detailed estimates of historical changes in Egyptian HCV prevalence. Because our results are consistent with a demographic scenario specified a priori, they also provide an objective test of inference methods based on the coalescent process.     

Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention

The burden of hepatocellular carcinoma (HCC) has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. This has been attributed to several biological (e.g. hepatitis B and C virus infection) and environmental factors (e.g. aflatoxin, AF). Other factors such as cigarette smoking, occupational exposure to chemicals such as pesticides, and endemic infections in the community, such as schistosomiasis, may have additional roles in the etiology or progression of the disease. Estimates of the burden of cancer caused by these factors provide an opportunity for prevention. Previously, there was strong evidence that hepatitis B virus (HBV) was the major cause of HCC in Egypt, but more recently HCV has become the predominant factor associated with the more recent epidemic of HCC. It has been well documented that Egypt has one of the highest prevalence rates of HCV infection in the world. The natural history of HCV infection and disease progression, however, are influenced by additional factors such as duration of infection, age at infection, sex, co-infection with HBV, the level of HCV viraemia and its genotype. The role of exposure to aflatoxins and development of HCC in Egypt was historically less clear. Nevertheless, recent food sampling surveys and population-based studies indicated that exposure to aflatoxins in Egypt may have been underestimated in the past. Recent results indicated that both local and imported samples were positive for aflatoxin B1 (AFB1, 17.5% and 20%, respectively), with concentrations ranging from 3 to 25 microg/kg. The level of AFB1 was dependent on the area of collection as well as the season of the year. In a population-based study, the level and frequency of aflatoxin M1 (AFM1, a major metabolite of aflatoxin B1 excreted in breast milk) was assessed as a biomarker of maternal exposure. The samples were collected from a selected group of 388 Egyptian lactating mothers during May-September 2003. Non-working status, obesity, high corn oil consumption, and the number of offspring contributed to the variability in occurrence of AFM1 in breast milk. Prevention and intervention approaches directed to risk factors of HCC can play a critical role in its prevention. In the case of HCV infection a prevention programme can be achieved by changing personal behaviors and/or cultural habits which are risk factors for HCV transmission, such as injection with contaminated syringes, blood transfusion, surgical operations, venous catheterization, use of common syringes, dental treatment and circumcision at home. Prevention of exposure to aflatoxins can be achieved either at community (via good agriculture practices) or individual levels (treatment or dietary interventions). In conclusion, due to the alarming increase in the incidence of HCC in Egypt, there is a need to further investigate the contribution of these emerging risk factors to the development of HCC in Egypt. This may enable us to determine the susceptibility to HCC among high-risk groups and to provide these individuals with effective measures for early prevention or intervention.     

The USAID/Government of Egypt's Schistosomiasis Research Project (SRP)

Schistosomiasis is the major public health problem in rural Egypt, with almost six million Egyptians infected as at mid-1996. In 1983, the prevalence of schistosomiasis in rural Egypt was greater than 50%, but a ten-year campaign of diagnosis and treatment has reduced the prevalence and intensity of infection. Parallel to this campaign, the government of the USA has funded a research project to examine all aspects of schistosomiasis with a view to improving the control strategy. As outlined here by Taha El Khoby, Nabil Galal and Alan Fenwick, after almost ten years, the project's achievements include: assisting WHO in its attempts to develop a vaccine against schistosomiasis, developing a suspension formulation of praziquantel suitable for young children, and establishing a unit to monitor reports of resistance to praziquantel. In addition, a large epidemiological study has established the extent of the problem in Egypt. Slow-release formulation of niclosamide, health education material for use on TV, dipstick diagnostic tests, and evaluation of ultrasound as a diagnostic tool have also been achieved. As the project closes, Egypt is left with an effective strategy for the control of schistosomiasis and several back-up tools for use in the event of development of resistance to praziquantel. The Ministry of Health and Population has the basis of a Geographical Information System (GIS) unit and the country has a trained and equipped scientific community capable of biomedical research, and almost 100 scientific papers published on their work.     

Therapeutic Potential of Myrrh and Ivermectin against Experimental Trichinella spiralis Infection in Mice

Trichinosis is a parasitic zoonosis caused by the nematode Trichinella spiralis. Anthelmintics are used to eliminate intestinal adults as well as tissue-migrating and encysted larvae. This study aimed to investigate the effects of ivermectin and myrrh obtained from the aloe-gum resin of Commiphora molmol on experimental trichinosis. Ninety albino mice were orally infected with 300 T. spiralis larvae. Drugs were tested against adult worms at day 0 and day 5 and against encysted larvae on day 15 and day 35 post-infection (PI). Mature worms and encysted larvae were counted in addition to histopathological examination of muscle specimens. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, albumin, globulin, urea, and creatinine values were estimated. Significant reductions in mean worm numbers were detected in ivermectin treated mice at day 0 and day 5 PI achieving efficacies of 98.5% and 80.0%, while efficacies of myrrh in treated mice were 80.7% and 51.5%, respectively. At days 15 and 35 post-infection, ivermectin induced significant reduction in encysted larval counts achieving efficacies of 76.5% and 54.0%, respectively, while myrrh efficacies were 76.6% and 35.0%, respectively. AST, ALT, urea, and creatinine levels were reduced, while total proteins were increased in response to both treatments compared to their values in the infected non-treated mice. Ivermectin use for controlling T. spiralis could be continued. Myrrh was effective and could be a promising drug against the Egyptian strains of T. spiralis with results nearly comparable to ivermectin.     

Novel Phylogenetic Algorithm to Monitor Human Tropism in Egyptian H5N1-HPAIV Reveals Evolution toward Efficient Human-to-Human Transmission

Years of endemic infections with highly pathogenic avian influenza (HPAI) A subtype H5N1 virus in poultry and high numbers of infections in humans provide ample opportunity in Egypt for H5N1-HPAIV to develop pandemic potential. In an effort to better understand the viral determinants that facilitate human infections of the Egyptian H5N1-HPAIVvirus, we developed a new phylogenetic algorithm based on a new distance measure derived from the informational spectrum method (ISM). This new approach, which describes functional aspects of the evolution of the hemagglutinin subunit 1 (HA1), revealed a growing group G2 of H5N1-HPAIV in Egypt after 2009 that acquired new informational spectrum (IS) properties suggestive of an increased human tropism and pandemic potential. While in 2006 all viruses in Egypt belonged to the G1 group, by 2011 these viruses were virtually replaced by G2 viruses. All of the G2 viruses displayed four characteristic mutations (D43N, S120(D,N), (S,L)129Δ and I151T), three of which were previously reported to increase binding to the human receptor. Already in 2006–2008 G2 viruses were significantly (p<0.02) more often found in humans than expected from their overall prevalence and this further increased in 2009–2011 (p<0.007). Our approach also identified viruses that acquired additional mutations that we predict to further enhance their human tropism. The extensive evolution of Egyptian H5N1-HPAIV towards a preferential human tropism underlines an urgent need to closely monitor these viruses with respect to molecular determinants of virulence.     

紫威科植物猫爪藤化学成分与生物活性研究进展

紫威科植物猫爪藤常被用作装饰植物,其自然群落主要分布在热带美洲的一些国家,在其它国家移植或归化的猫爪藤因被认为具有生物入侵危害而备受关注。然而,在原产地的一些国家或地区民间则将其作为药物治疗许多病症,如炎症、风湿病、痢疾、性病、疟疾、毒蛇咬伤等。近年来,这些国家的研究者就此对猫爪藤进行了较多的化学成分和药理作用的相关研究,本文主要综述了这方面的研究进展,以期使人们进一步了解猫爪藤具有药用价值的一面,从而引导和促进对其进行开发和利用而不要简单的当作有害入侵物种来进行对待。     

Fasciola gigantica: larval productivity of three different miracidial isolates in the snail Lymnaea truncatula

Bimiracidial infections of Lymnaea truncatula with three isolates of Fasciola gigantica, originating from China, Egypt and Madagascar, were carried out to determine the effect of geographic origin of the parasite on the larval productivity of redial generations. The prevalences of experimental infections in snails exposed to strains from Madagascar, China and Egypt were 20.8%, 60.0% and 80.0%, respectively. At day 49 post-exposure (p.e.), the total number of free rediae in snails infected with the Egyptian isolate was significantly higher than that recorded in the Madagascan group. On the other hand, at day 49 p.e., the majority of cercariae in the Chinese and Egyptian groups were produced by R2a rediae (70.6% and 66.6% of cercariae produced by all live rediae), while, in the Madagascan group, the cercariae were produced mainly by the first redial generation. Snails infected with the Egyptian isolate of miracidia developed more live rediae and, consequently, could produce a higher number of cercariae. As a result, L. truncatula snails were highly adapted to infections with the Egyptian and Chinese isolates of F. gigantica.     

Offline Controlling of Pseudomonas aeruginosa Resistant to protein Inhibitor Antibiotics Using Combination of EDTA and Na- citrate or Disinfectant (s)

P·aeruginosahave a number of virulence factors like extracellular toxins[1], protea-ses[2,3], haemolysins[4,5], and exopolysaccharide[6,7], which adapt the infection of specifichost tissues[8], causing severe problems·P·aeruginosacan survive in a numbe…     

Genotyping natural infections of Schistosoma mansoni in Biomphalaria alexandrina from Damietta, Egypt, with comparisons to natural snail infections from Kenya

The distribution of Schistosoma genotypes among individuals in snail populations provides insights regarding the dynamics of transmission and compatibility between schistosome and snail hosts. A survey of Biomphalaria alexandrina from Damietta (Nile Delta, Egypt), an area subjected to persistent schistosomiasis control efforts, provided only 17 snails infected with Schistosoma mansoni (6.1% overall prevalence), each shown by microsatellite analysis to have a single genotype infection. By contrast, recent studies of uncontrolled S. mansoni transmission foci in Kenya revealed that 4.3% Biomphalaria pfeifferi and 20-25% Biomphalaria sudanica snails had multiple genotype infections. Compared with the 3 Kenyan populations, the Egyptian population of S. mansoni also showed a lesser degree of genetic variability and was genetically differentiated from them. We suggest that tracking of genotype diversity in infected snails could be further developed to serve as an additional and valuable independent indicator of efficacy of schistosomiasis control in Egypt and elsewhere.     

Towards control of schistosomiasis in sub-Saharan Africa

Approximately 80% of the 200 million people infected with schistosomiasis inhabit sub-Saharan Africa, and the annual mortality is estimated to be 280,000. Praziquantel is the drug of choice in the treatment of schistosomiasis and pregnant women may now be treated. It was agreed at the World Health Assembly in 2001 that at least 75% of school-aged children in high burden areas should be treated for schistosomiasis and soil-transmitted helminth infections by 2010 to reduce morbidity. A grant from the Bill and Melinda Gates Foundation to the Schistosomiasis Control Initiative, Imperial College of Science, Technology and Medicine, London has enabled control programmes to be initiated in Uganda, Tanzania, Zambia, Burkina Faso, Niger and Mali. Additional programmes have recently commenced in Zanzibar with a grant from the Health Foundation to The Natural History Museum, London and in Cameroon. Combination treatment for schistosomiasis, gastrointestinal helminths and filariasis reduces costs of control programmes. The EC Concerted Action Group on 'Praziquantel: its central role in the chemotherapy of schistosome infection' met in Yaoundé Cameroon in 2004 to discuss recent developments in laboratory and field studies. The use of standard operating procedures will enable data on drug action on schistosomes produced in different laboratories to be compared. With the ever increasing use of praziquantel there is a possibility of the development of resistance by schistosomes to the drug, hence the necessity to explore the activities of other compounds. Artemether, unlike praziquantel, is effective against immature schistosomes. The effectiveness of mirazid, an extract of myrrh, is controversial as data from different laboratories are equivocal. It is suggested that an independent body such as the World Health Organization should determine whether mirazid should be used in the treatment of schistosomiasis.     

具核梭杆菌与全身疾病相关性的研究进展

具核梭杆菌(Fusobacterium nucleatum,F.nucleatum)是在口腔微生态环境中常驻的一种革兰阴性专性厌氧菌,近来研究发现F.nucleatum不仅与口腔感染性疾病如牙周病、根尖周病等的发生、发展密切相关,而且与早产低体重儿、结直肠癌、呼吸道感染等全身疾病密切相关。本研究对F.nucleatum生物学功能及与口腔感染、全身疾病相关性的研究进展作一综述。     

The additive and synergistic antimicrobial effects of select frankincense and myrrh oils--a combination from the pharaonic pharmacopoeia

Aims: The in vitro antimicrobial activity of three essential oil samples of frankincense (Boswellia rivae, Boswellia neglecta and Boswellia papyrifera) and two essential oil samples of myrrh and sweet myrrh (Commiphora guidotti and Commiphora myrrha), collected from different regions of Ethiopia, was investigated independently and in combination to determine their anti‐infective properties. Methods and Results: The microdilution minimum inhibitory concentration (MIC) assay was performed, whereby it was noted that generally Cryptococcus neoformans (MIC values in the range of 0·8–1·4 mg ml^?1) and Pseudomonas aeruginosa (MIC values in the range of 0·5–1·3 mg ml^?1) often appeared to be the most susceptible micro‐organisms against oils of both Boswellia and Commiphora spp. When assayed in various combinations, the frankincense and myrrh oils displayed synergistic, additive and noninteractive properties, with no antagonism noted. When investigating different ratio combinations against Bacillus cereus, the most favourable combination was between B. papyrifera and C. myrrha. The composition of the oils was determined by gas chromatography coupled to mass spectrometry (GC–MS) to document the specific chemotypes used in the study, and the chemical profiles were found to be congruent with previously reported data. Conclusions: The majority of interactions identified synergistic and additive effects, with strong synergism noted between B. papyrifera and C. myrrha. Significance and Impact of the Study: Frankincense and myrrh essential oils have been used in combination since 1500 bc ; however, no antimicrobial investigations have been undertaken to confirm their effect in combination. This study validates the enhanced efficacy when used in combination against a selection of pathogens.     

Radix natalensis (Gastropoda: Lymnaeidae), a potential intermediate host of Fasciola hepatica in Egypt

Experimental infections of Egyptian Radix natalensis with French miracidia of Fasciola hepatica were carried out to determine if this snail might act as an intermediate host in the life cycle of this digenean in Egypt. Single exposures of R. natalensis to miracidia (2/snail) and two successive exposures (a total of 4 miracidia/ snail) were performed using lymnaeids measuring 1 to 6 mm in height. Live larval forms of F. hepatica were noted in single- and double-exposed snails. In double exposures, a significant increase of snail survival on day 28 post-exposure (at 24 degrees C) and an decrease in prevalence were noted when the height of snails at exposure was increasing. Cercariae of F. hepatica were shed by these snails (90.7/snail) during a mean patent period of 24.3 days. All snails have released these cercariae during 2-13 waves of shedding. According to these results, R. natalensis can be considered a potential intermediate host of F. hepatica in Egypt.     

Neglected tropical diseases of the Middle East and North Africa: review of their prevalence, distribution, and opportunities for control

The neglected tropical diseases (NTDs) are highly endemic but patchily distributed among the 20 countries and almost 400 million people of the Middle East and North Africa (MENA) region, and disproportionately affect an estimated 65 million people living on less than US$2 per day. Egypt has the largest number of people living in poverty of any MENA nation, while Yemen has the highest prevalence of people living in poverty. These two nations stand out for having suffered the highest rates of many NTDs, including the soil-transmitted nematode infections, filarial infections, schistosomiasis, fascioliasis, leprosy, and trachoma, although they should be recognized for recent measures aimed at NTD control. Leishmaniasis, especially cutaneous leishmaniasis, is endemic in Syria, Iran, Iraq, Libya, Morocco, and elsewhere in the region. Both zoonotic (Leishmania major) and anthroponotic (Leishmania tropica) forms are endemic in MENA in rural arid regions and urban regions, respectively. Other endemic zoonotic NTDs include cystic echinococcosis, fascioliasis, and brucellosis. Dengue is endemic in Saudi Arabia, where Rift Valley fever and Alkhurma hemorrhagic fever have also emerged. Great strides have been made towards elimination of several endemic NTDs, including lymphatic filariasis in Egypt and Yemen; schistosomiasis in Iran, Morocco, and Oman; and trachoma in Morocco, Algeria, Iran, Libya, Oman, Saudi Arabia, Tunisia, and the United Arab Emirates. A particularly noteworthy achievement is the long battle waged against schistosomiasis in Egypt, where prevalence has been brought down by regular praziquantel treatment. Conflict and human and animal migrations are key social determinants in preventing the control or elimination of NTDs in the MENA, while local political will, strengthened international and intersectoral cooperative efforts for surveillance, mass drug administration, and vaccination are essential for elimination.     

Optimization of Benzoisothiazole dioxide inhibitory activity of the NS5B polymerase of HCV genotype 4 using ligand-steered homological modeling, reaction-driven scaffold-hopping and Enovo workflow

Infection caused by hepatitis C virus (HCV) is a significant world health problem for which novel therapies are in urgent demand. The virus is highly prevalent in the Middle East and Africa particularly Egypt with more than 90% of infections due to genotype 4. Nonstructural (NS5B) viral proteins have emerged as an attractive target for HCV antivirals discovery. A potent class of inhibitors having benzisothiazole dioxide scaffold has been identified on this target, however they were mainly active on genotype 1 while exhibiting much lowered activity on other genotypes due to the high degree of mutation of its binding site. Based on this fact, we employed a novel strategy to optimize this class on genotype 4. This strategy depends on using a refined ligand-steered homological model of this genotype to study the mutation binding energies of the binding site amino acid residues, the essential features for interaction and provide a structure-based pharmacophore model that can aid optimization. This model was applied on a focused library which was generated using a reaction-driven scaffold-hopping strategy. The hits retrieved were subjected to Enovo pipeline pilot optimization workflow that employs R-group enumeration, core-constrained protein docking using modified CDOCKER and finally ranking of poses using an accurate molecular mechanics generalized Born with surface area method.     

An overview of aquaculture in eastern Africa

Egypt, Kenya and Malawi, have the earliest recorded history of fish farming in eastern Africa, dating back to the beginning of the century. Between 1940 and 1960 aquaculture started in Rwanda, Uganda Zambia, Zimbabwe and Tanzania in that order. Overall, Egypt is the leader in aquaculture development in the region with an estimated annual production of 24 000t (1982), followed by Zambia, 1680t (1967), then Kenya, 1085t (1985). The main aquaculture systems in practice are: monoculture, polyculture, using tilapia as the main species, mono or polyculture of tilapia with animal husbandry and rice-cum-fish culture. Aquaculture research and training are carried out in Universities, research institutions and Government Fisheries Training colleges. The major common constraints to aquaculture development are biological, infrastructural and economic.