Microbes have made a phenomenal contribution to the health and well-being of people throughout the world. In addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. This review centers on these beneficial secondary metabolites, the discovery of which goes back 80 years to the time when penicillin was discovered by Alexander Fleming.

/pdf/microbial-drug-discovery-80-years-of-progress-2u89dilx0f.pdf

Microbial drug discovery: 80 years of progress

Strongyloides stercoralis infects 30 million people in 70 countries. Infection usually results in asymptomatic chronic disease of the gut, which can remain undetected for decades. However, in patients receiving long-term corticosteroid therapy, hyperinfection can occur, resulting in high mortality rates (up to 87%). Strongyloidiasis is difficult to diagnose because the parasite load is low and the larval output is irregular. Results of a single stool examination by use of conventional techniques fail to detect larvae in up to 70% of cases. Several immunodiagnostic assays have been found ineffective in detecting disseminated infections and show extensive cross-reactivity with hookworms, filariae, and schistosomes. Although it is important to detect latent S. stercoralis infections before administering chemotherapy or before the onset of immunosuppression in patients at risk, a specific and sensitive diagnostic test is lacking. This review describes the clinical manifestations of strongyloidiasis, as well as various diagnostic tests and treatment strategies.

http://www.iacld.ir/DL/elm/diagnosisofstrongyloidesstercoralisinfection.pdf

Diagnosis of Strongyloides stercoralis Infection

The soil-transmitted threadworm, Strongyloides stercoralis, is one of the most neglected among the so-called neglected tropical diseases (NTDs). We reviewed studies of the last 20 years on S. stercoralis's global prevalence in general populations and risk groups.; A literature search was performed in PubMed for articles published between January 1989 and October 2011. Articles presenting information on infection prevalence were included. A Bayesian meta-analysis was carried out to obtain country-specific prevalence estimates and to compare disease odds ratios in different risk groups taking into account the sensitivities of the diagnostic methods applied. A total of 354 studies from 78 countries were included for the prevalence calculations, 194 (62.4%) were community-based studies, 121 (34.2%) were hospital-based studies and 39 (11.0%) were studies on refugees and immigrants. World maps with country data are provided. In numerous African, Asian and South-American resource-poor countries, information on S. stercoralis is lacking. The meta-analysis showed an association between HIV-infection/alcoholism and S. stercoralis infection (OR: 2.17 BCI: 1.18-4.01; OR: 6.69; BCI: 1.47-33.8), respectively.; Our findings show high infection prevalence rates in the general population in selected countries and geographical regions. S. stercoralis infection is prominent in several risk groups. Adequate information on the prevalence is still lacking from many countries. However, current information underscore that S. stercoralis must not be neglected. Further assessments in socio-economic and ecological settings are needed and integration into global helminth control is warranted.

https://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0002288&type=printable

Strongyloides stercoralis: Global Distribution and Risk Factors.

Blastocystis hominis is a unicellular organism found commonly in the intestinal tract of humans and many other animals. Very little is known of the basic biology of the organism, and controversy surrounds its taxonomy and pathogenicity. There morphological forms (vacuolar, granular, and ameboid) have been recognized, but recent studies have revealed several additional forms (cyst, avacuolar, and multivacuolar). The biochemistry of the organism has not been studied to any extent, and organelles and structures of unknown function and composition are present in the cells. Several life cycles have been proposed but not experimentally validated. The form used for transmission has not been defined. Infections with the organism are worldwide and appear in both immunocompetent and immunodeficient individuals. Symptoms generally attributed to B. hominis infection are nonspecific, and the need for treatment is debated. If treatment appears warranted, metronidazole is suggested as the drug of choice, although failures of this drug in eradicating the organism have been reported. Infection is diagnosed by light microscopic examination of stained smears or wet mounts of fecal material. Most laboratories identify B. hominis by observing the vacuolar form, although morphological studies indicate that other forms, such as the cyst form and multivacuolar form, also should be sought for diagnosis.

Blastocystis hominis revisited.

Analysis of the gene cluster from Streptomyces avermitilis that governs the biosynthesis of the polyketide anthelmintic avermectin revealed that it contains four large ORFs encoding giant multifunctional polypeptides of the avermectin polyketide synthase (AVES 1, AVES 2, AVES 3, and AVES 4). These clustered polyketide synthase genes responsible for avermectin biosynthesis together encode 12 homologous sets of enzyme activities (modules), each catalyzing a specific round of polyketide chain elongation. The clustered genes encoding polyketide synthase are organized as two sets of six modular repeats, aveA1-aveA2 and aveA3-aveA4, which are convergently transcribed. The total of 55 constituent active sites makes this the most complex multifunctional enzyme system identified to date. The sequenced DNA region contains 14 additional ORFs, some of which encode polypeptides governing other key steps in avermectin biosynthesis. Between the two sets of polyketide synthase genes lie two genes involved in postpolyketide modification, one of which encodes cynthochrome P450 hydroxylase that probably catalyzes furan ring formation at C6 to C8a. Immediately right of the large polyketide synthase genes is a set of genes involved in oleandrose biosynthesis and its transglycosylation to polyketide-derived aglycons. This cluster includes nine genes, but one is not functional in the biosynthesis of avermectin. On the left side of polyketide synthase genes, two ORFs encoding methyltransferase and nonpolyketide synthase ketoreductase involved in postpolyketide modification are located to the left of the polyketide synthase genes, and an adjacent gene encodes a regulatory function that may be involved in activation of the transcription of avermectin biosynthetic genes.

https://www.pnas.org/content/pnas/96/17/9509.full.pdf

Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in streptomyces avermitilis

Agar-plate culture of feces using a modified petri dish proved to be highly efficient in the detection of Strongyloides stercoralis infection Furrows left by S stercoralis on the agar plate were distinguished readily in size from those left by Necator americanus

Efficacy of agar-plate culture in detection of Strongyloides stercoralis infection.

A new method for the detection of Strongyloides larvae was established. A small amount of stool was placed in the center of an agar plate and was incubated at 37°C for 24 hr. Characteristically aligned bacterial colonies or furrows left by crawling Strongyloides larvae appeared on the agar surface are the positive findings. The larvae gathered in a well made on positive plate were identified. By using this method, Strongyloides was detected in 46 cases (4.5%) out of 1, 017 healthy adults. Whereas, it was detected in 0 and 3 cases (0 and 0.3%) by direct stool smear method and filter paper technique, respectively. Examination of 246 cases by this agar plate method and formalinether method (MGL) revealed that 14 cases (5.7%) were positive by the former and 2 cases (0.8%) by the latter. Agar plate method is not laborious nor expensive, and recommendable for mass examination and for the detection of asymptomatic carriers.

A new method to detect strongyloides stercoralis from human stool

Okinawa Prefecture is an endemic area of Strongyloides stercoralis infection. Since treatment of this infection remains unsatisfactory, we evaluated the efficacy of ivermectin. Twenty-three patients were treated with a single oral dose of ivermectin (mean +/- SD, 105.5 +/- 20.8 mcg/kg of body weight), followed by a second dose two weeks later. The rate of cure was 85.7% at 2 weeks after the first treatment, and 90.5% at 2 weeks after the second treatment. Side effects occurred in 2 patients (8.7%), but they were mild and transient. The results indicate that ivermectin might be useful and relatively safe for the therapy of Strongyloides stercoralis infection as an alternative to thiabendazole or mebendazole.

Efficacy of ivermectin against Strongyloides stercoralis in humans.

A 36-year-old woman with ulcerative colitis presented with fever, chest and back pain, and fatigue sensation of the arm. Her upper limb pulses were absent. Angiography showed multiple aneurysms of the aorta and its branches, consistent with Takayasu's arteritis. She showed HLA-B35 but no B52, which is the typical haplotype among the coexistence cases of both diseases. Prednisolone was effective. The possible pathogenic association of the disorders is discussed.

Pulseless hematochezia: Takayasu's arteritis associated with ulcerative colitis.

To assess the concomitance of strongyloidiasis and HTLV-1 infection, an epidemiological survey was conducted in Okinawa, Japan, using the agar-plate culture, a highly sensitive method for detection of Strongyloides stercoralis. No significant difference in the positive rate of anti-HTLV-1 antibody was found between Strongyloides carriers and non-carriers. This result suggests that these two infections occur independently

Tamiki Arakaki

Papers

Efficacy of agar-plate culture in detection of Strongyloides stercoralis infection.

A new method to detect strongyloides stercoralis from human stool

Efficacy of ivermectin against Strongyloides stercoralis in humans.

Pulseless hematochezia: Takayasu's arteritis associated with ulcerative colitis.

Is the prevalence of HTLV-1 infection higher in Strongyloides carriers than in non-carriers?