Abu Hamed, Sudan, the northernmost location of onchocerciasis in the world, began community-directed treatment with ivermectin (CDTI) in 1998, with annual treatments enhanced to semiannual in 2007. We assessed the status of the parasite transmission in 2011 entomologically, parasitologically, and serologically. O-150 pool screening showed no parasite DNA in 17,537 black flies collected in 2011 (95% confidence interval upper limit [95% CI UL] = 0.023). Skin microfilariae, nodules, and signs of skin disease were absent in 536 individuals in seven local communities. Similarly, no evidence of Onchocerca volvulus Ov16 antibodies was found in 6,756 school children ≤ 10 years (95% CI UL = 0.03%). Because this assessment of the focus meets the 2001 World Health Organization (WHO) criteria for interrupted transmission, treatment was halted in 2012, and a post-treatment surveillance period was initiated in anticipation of declaration of disease elimination in this area. We provide the first evidence in East Africa that long-term CDTI alone can interrupt transmission of onchocerciasis.
Abu Hamed, the northernmost onchocerciasis focus in the world, is located along the River Nile banks in the Nubian Desert. Hydroelectric dams can alter activity of black flies and may provide breeding sites for black fly. Merowe Dam, the largest hydropower project in Africa, was built west of Abu Hamed focus in 2009. The impact of the Dam on onchocerciasis and its black fly vectors in Abu Hamed focus was measured in this study.
Entomological surveys for aquatic stages and adult Simulium hamedense were conducted before and after the inception of Merowe Dam in 2007/2008 and 2010/2011. There was no black fly breeding or adult activity in the previously known breeding sites upstream of the Merowe Dam with the western most breeding site found in AlSarsaf village near the center of the focus. No adult or aquatic stages of black flies were found downstream of the Dam.
The artificial lake of the Dam flooded all the breeding sites in the western region of the focus and no aquatic stages and/or adult black fly activity were established in the study area upstream of the Dam. The Dam seems to have positive impact on onchocerciasis and its black fly vectors in Abu Hamed focus. These outcomes of the Merowe Dam might have contributed to the recently declared interruption of onchocerciasis transmission in Abu Hamed focus. Continuous entomological surveys are needed to monitor presence of black fly vectors and its impact on the disease.
Onchocerciasis; Elimination; Merowe Dam; Abu Hamed focus; Simulium hamedense; Sudan
A new series of 2-pyrazolin-1-ylthiazoles 8a–d and 13–16 was synthesized by cyclization of N-thiocarboxamide-2-pyrazoline with different haloketones and 2,3-dichloroquinoxaline. The structures of the new compounds were confirmed by elemental analyses as well as NMR, IR, and mass spectral data. The newly synthesized compounds were evaluated for their antimicrobial activities, and also their minimum inhibitory concentration (MIC) against most of test organisms was performed. Amongst the tested ones, compound 8c displayed excellent antimicrobial activity.
In the title compound, C24H17BrFN3S, the pyrazole ring is almost planar (r.m.s. deviation = 0.043 Å), with all but the perpendicular fluorobenzene ring substituents [dihedral angle = 77.9 (3)°] being very approximately coplanar [dihedral angle with the 2-thienyl ring = 19.4 (3)° and with the bromobenzene ring = 20.3 (3)°; dihedral angle between the 2-thienyl and attached phenyl ring = 11.0 (4)°], so that the molecule has a T-shape. In the crystal, supramolecular chains along the b-axis direction are sustained by C—H⋯S and C—Br⋯π interactions.
With respect to the triazole ring in the title compound, C19H16FN3O, the p-tolyl ring is inclined [dihedral angle = 51.79 (11)°], whereas the chalcone residue is almost coplanar [O—C—C—N and C—C—C—C torsion angles = −178.71 (19) and 178.42 (18)°, respectively]. The conformation about the C=C bond [1.328 (3) Å] is E, and the triazole methyl group and the carbonyl O atom are syn. In the crystal, centrosymmetrically related molecules are connected by π–π interactions between the triazole and p-tolyl rings [centroid–centroid distance = 3.6599 (12) Å] and these are linked into a three-dimensional architecture by C—H⋯N and C—H⋯π interactions.
In the title compound, C18H14N6O2, the benzene ring is slightly twisted out of the plane of the 1,2,3-triazole ring (r.m.s. deviation = 0.010 Å), forming a dihedral angle of 6.20 (13)°. The nine non-H ring atoms of the fused five- and six-membered ring system are almost coplanar (r.m.s. deviation = 0.032 Å). The near coplanarity in the central residue is consolidated by an intramolecular bifurcated N—H⋯(O,N) hydrogen bond. The conformation about the N=C bond is Z. In the crystal, supramolecular chains along  are sustained by N—H⋯O hydrogen bonds and C—H⋯O interactions. These are consolidated into a three-dimensional architecture by C—H⋯π and π–π interactions; the latter occur between centrosymmetrically related 1,2,3-triazole rings [centroid–centroid distance = 3.6056 (14) Å].
In the title compound, C14H13N3O3, a twist occurs, as seen in the dihedral angle of 53.60 (12)° between the pyrrole and benzene rings. A three-dimensional architecture is formed in the crystal whereby layers of molecules in the ac plane are connected by C—H⋯O and C—H⋯π interactions.
In the title compound, C16H13ClFN3S, the pyrazole ring adopts an envelope conformation with the methine C atom being the flap atom. The chloro- and fluorobenzene rings are twisted out of the plane of the pyrazole ring [dihedral angles = 15.12 (11) and 80.55 (10)°, respectively]. The amine group is orientated towards a ring N atom, forming an intramolecular N—H⋯N hydrogen bond. This H atom also forms a hydrogen bond to the F atom, which along with N—H⋯S hydrogen bonding leads to a supramolecular chain along the c axis. Connections between chains of the type Cl⋯π lead to a layer in the bc plane.
In the title compound, C25H20FN3S, two independent molecules comprise the asymmetric unit, which differ in the relative orientation of the fluorobenzene ring with respect to the pyrazole ring to which it is attached [dihedral angles = 89.39 (17) and 75.23 (16)° in the two molecules]. Each pyrazole ring adopts an envelope conformation with the methine C atom being the flap atom. There are additional twists in the molecules, e.g. between the five-membered rings [dihedral angles = 18.23 (16) and 17.84 (16)°] and between the thiazole and attached phenyl ring [10.26 (16) and 20.87 (15)°]. Overall, each molecule has a T-shape. In the crystal, molecules are connected into a three-dimensional architecture by weak C—H⋯π interactions.
The central pyrazole ring in the title compound, C17H16FN3S, adopts an envelope conformation with the methine C atom bearing the 4-fluorophenyl substituent as the flap atom. Whereas the tolyl ring is slightly twisted out of the least-squares plane through the pyrazole ring [dihedral angle = 13.51 (11)°], the fluorobenzene ring is almost perpendicular [dihedral angle = 80.21 (11)°]. The thioamide group is almost coplanar with the N—N bond of the ring [N—N—C—N torsion angle = 1.2 (3)°] and the amine group forms an intramolecular hydrogen bond with a ring N atom. In the crystal, supramolecular double layers in the bc plane are formed via N—H⋯S, N—H⋯F and C—H⋯F interactions.
In the title compound, C18H13Cl2N3OS, the eight atoms comprising the central imidazo/thiadiazolethiadiazole residue are coplanar (r.m.s. deviation = 0.009 Å). The dihedral angle of 8.72 (13)° between the dichlorobenzene and tolyl rings reflects a twist about the O—C(benzene) bond; the Cm—O—Cb—Cb torsion angle = −168.5 (2)° (m = methylene C and b is benzene C). Supramolecular tapes along the b axis are found in the crystal structure which are mediated by π–π interactions occurring between centrosymmetrically related thiadiazole rings [inter-ring centroid distance = 3.6907 (16) Å] and between the benzene and tolyl rings [inter-ring centroid distance = 3.7597 (16) Å].
The essentially planar pyrazole ring (r.m.s. deviation = 0.013 Å) in the title hemisolvate, C31H33N7S·0.5C3H7NO, is almost coplanar with the pendant thiourea residue [N—N—C—S torsion angle = −173.2 (4)°] and slightly twisted with respect to the triazole ring [dihedral angle = 7.7 (3)°]. An intramolecular thiourea–pyrazole N—H⋯N hydrogen bond, via an S(5) loop, is formed. Supramolecular chains along the c axis are formed in the crystal via piperidine–triazole C—H⋯N interactions. These are bridged into loosely associated double chains via C—H⋯O interactions involving the disordered (over two positions) dimethylformamide solvent molecules. The thiourea-bound phenyl ring is also disordered over two positions of equal occupancy.
In the title compound, C28H22BrFN6S, the central pyrazole ring has an envelope conformation, with the methine C atom being the flap atom. The dihedral angles between the least-squares plane through this ring and the adjacent thiazole [18.81 (15)°] and triazole [1.83 (16)°] rings indicate a twist in the molecule. A further twist is evident by the dihedral angle of 64.48 (16)° between the triazole ring and the attached benzene ring. In the crystal, C—H⋯N, C—H⋯F, C—H⋯π and π–π interactions [occurring between the thiazole and triazole rings, centroid–centroid distance = 3.571 (2) Å] link molecules into a three-dimensional architecture. The sample studied was a non-merohedral twin; the minor twin component refined to 47.16 (7)%.
Onchocerciasis remains an important debilitating disease in many areas of Africa, including Sudan. The status of infection transmission in 2007 was assessed in the vectors of two disease foci in Sudan: Abu Hamed in northern Sudan, which has received at least 10 years of annual treatment and Galabat focus in eastern Sudan, where only minor, largely undocumented treatment activity has occurred. Assessment of more than 30,000 black flies for Onchocerca volvulus infectious stage L3 larvae by using an O-150 polymerase chain reaction protocol showed that black fly infectivity rates were 0.84 (95% confidence interval = 0.0497–1.88) per 10,000 flies for Abu Hamed and 6.9 (95% confidence interval = 1.1–16.4) infective flies per 10,000 for Galabat. These results provide entomologic evidence for suppressed Onchocerca volvulus transmission in the Abu Hamed focus and a moderate transmission rate of the parasite in the Galabat focus.