Progress Towards Elimination of Trachoma in Kenya 2017-2020.

PURPOSE: Trachoma is endemic in Kenya. Since baseline trachoma surveys in 2004, a concerted programme has been undertaken to reduce the prevalence of disease. Here, we report on trachoma prevalence surveys carried out between 2017 and 2020 after interventions were implemented in some areas for trachoma elimination purposes. METHODS: A total of 48 cross-sectional population-based trachoma prevalence surveys were conducted in 39 evaluation units (EUs; covering 45 subcounties) of Kenya between 2017 and 2020. Thirty EUs were surveyed once and nine EUs were surveyed twice over this period. Individuals ≥ 1 year old were assessed for trachomatous inflammation-follicular (TF), trachomatous inflammation-intense (TI) and trichiasis. Data were collected on household access to water, sanitation and hygiene (WASH). RESULTS: A total of 147,573 people were examined. At the end of 2020, in the 39 EUs surveyed, the prevalence of TF in 1-9-year-olds was ≥5% in 11 EUs and the prevalence of trichiasis unknown to the health system in individuals aged ≥15 years was ≥0.2% in 25 EUs. A small minority of households (median <50% for all indicators) had access to improved WASH facilities. CONCLUSION: Kenya has made excellent progress towards elimination of trachoma as a public health problem. However, there is more work to do. Between one and three rounds of antibiotic mass drug administration are required in 11 EUs. Sustained investment in surgical provision, continued TT case-finding, promotion of facial cleanliness and environmental improvement are required throughout the surveyed area.

Isolation of potassium salt of oxadiazole-2-thione and in vitro anticancer activities of its Cu(II) and Zn(II) complexes against MDA-MB-231 human breast carcinoma cells.

A potassium 4-(pyridyl)-1,3,4-oxadiazole-2-thione was isolated in a basic medium, and its complexes [Cu(en)2(pot)2] (1) and [Zn(en)2(pot)2]HBr·CH3OH (2) containing ethylenediamine (en) as secondary ligand were synthesized and fully characterized. Upon changing the reaction conditions, the Cu(II) complex (1) adopts an octahedral geometry around the metal center. The cytotoxic activity of ligand (Kpot·H2O) along with complexes 1 and 2 was tested, and their anticancer activity against MDA-MB-231 human breast cancer cells was demonstrated, with complex 1 exhibiting superior cytotoxicity against these cells as compared to Kpot·H2O and complex 2. According to the DNA nicking assay, the ligand (Kpot·H2O) was found to be more potent to scavenge hydroxyl radicals even at a lower concentration (50 µg mL-1) than that of both complexes. The wound healing assay revealed that ligand Kpot·H2O and its complexes 1 and 2 attenuated the migration of the above-mentioned cell line. The loss of cellular and nuclear integrity and induction in the activity of Caspase-3 suggest the anticancer potential of ligand Kpot·H2O and its complexes 1 and 2 against MDA-MB-231 cells.

Prevalence of Trachomatous Trichiasis in Ten Evaluation Units of Embu and Kitui Counties, Kenya.

BACKGROUND: Late-stage blinding sequalae of trachoma such as trachomatous trichiasis (TT) typically take decades to develop and often do so in the absence of ongoing ocular Chlamydia trachomatis infection. This suggests that most TT risk accumulates in early life; as a result, population-level TT incidence and prevalence can remain high years after C. trachomatis transmission among children has decreased. In Embu and Kitui counties, Kenya, the prevalence of trachomatous inflammation - follicular is low in children. In this survey, we set out to determine the prevalence of TT in ten evaluation units (EUs) in these counties. METHODS: We undertook ten cross-sectional prevalence surveys for TT. In each EU, people aged ≥15 years were selected by a two-stage cluster sampling method and examined for TT. Those with TT were asked questions on whether they had been offered management for it. Prevalence was adjusted to the underlying age and gender structure of the population. RESULTS: A total of 18,987 people aged ≥15 years were examined. Per EU, the median number of examined participants was 1,656 (range: 1,451 - 3,016) and median response rate was 86% (range: 81 - 95%). The prevalence of TT unknown to the health system in people aged ≥15 years was above the threshold for elimination (≥0.2%) in all ten EUs studied (range: 0.2-0.7%). TT was significantly more common in older than younger individuals and in women than in men. DISCUSSION: Provision of surgical services should be strengthened in Embu and Kitui counties of Kenya to achieve the World Health Organization threshold for eliminating TT as a public health problem.

Synthesis and absolute structure of (R)-2-(benzyl-selan-yl)-1-phenyl-ethanaminium hydrogen sulfate monohydrate: crystal structure and Hirshfeld surface analyses.

A hydrogen sulfate salt, C15H18NSe+·HSO4 -·H2O or [BnSeCH2CH(Ph)NH3 +](HSO4 -), of a chiral selenated amine (R)-2-(benzyl-selan-yl)-1-phenyl-ethan-amine (BnSeCH2CH(Ph)NH2) has been synthesized and characterized by elemental analysis,1H and 13C{1H} NMR, FT-IR analysis, and single-crystal X-ray diffraction studies. The title salt crystallizes in the monohydrate form in the non-centrosymmetric monoclinic P21 space group. The cation is somewhat W shaped with the dihedral angle between the two aromatic rings being 60.9 (4)°. The carbon atom attached to the amine nitro-gen atom is chiral and in the R configuration, and, the -C-C- bond of the -CH2-CH- fragment has a staggered conformation. In the crystal structure, two HSO4 - anions and two water mol-ecules form an R 4 4(12) tetra-meric type of assembly comprised of alternating HSO4 - anions and water mol-ecules via discrete D(2) O-H⋯O hydrogen bonds. This tetra-meric assembly aggregates along the b-axis direction as an infinite one-dimensional tape. Adjacent tapes are inter-connected via discrete D(2) N-H⋯O hydrogen bonds between the three amino hydrogen atoms of the cation sandwiched between the two tapes and the three HSO4 - anions of the nearest asymmetric units, resulting in a complex two-dimensional sheet along the ab plane. The pendant arrangement of the cations is stabilized by C-H⋯π inter-actions between adjacent cations running as chains down the [010] axis. Secondary Se⋯O [3.1474 (4) Å] inter-actions are also observed in the crystal structure. A Hirshfeld surface analysis, including d norm, shape-index and fingerprint plots of the cation, anion and solvent mol-ecule, was carried out to confirm the presence of various inter-actions in the crystal structure.

Dual sensing of methionine and aspartic acid in aqueous medium by a quinoline-based fluorescent probe.

A quinoline-based Schiff base sensor, 6-methyl-2-oxo-1,2-dihydro-quinoline-3-carboxaldehyde-4(N)-phenylsemicarbazone (6MPS), has been developed for selective sensing of methionine and aspartic acid in aqueous medium through "on-off-on" type selective detection of copper ion. Fluorescence imaging of 6MPS, 6MPSC, 6MPSCN, 6MPSC-met, 6MPSCN-met, 6MPSC-asp and 6MPSCN-asp has been successfully demonstrated, in which the sensing probes 6MPSC-met, 6MPSCN-met, 6MPSC-asp and 6MPSCN-asp displayed bright green fluorescence in both in vitro and in vivo live cells.

Rapid Whole Genome Sequencing of Serotype K1 Hypervirulent Klebsiella pneumoniae from an Undocumented Chinese Migrant.

BACKGROUND: Hypervirulent Klebsiella pneumoniae causes severe disseminated infections, typically with hepatic and central nervous system involvement including endophthalmitis. Case Presentation. We report a fatal case of an undocumented Chinese migrant in her 60s who presented to the emergency department with abdominal pain, lethargy, and headache over the preceding two weeks. She had a new diagnosis of diabetes mellitus on admission. Computed tomography scan of the thorax, abdomen, and pelvis showed bilateral pneumonia with liver abscesses. The patient was treated with empirical broad-spectrum antibiotics before K. pneumoniae was isolated from cerebrospinal fluid and blood cultures. The isolate was further characterised as a ST23 (ST: sequence type), serotype K1 hypervirulent strain using Nanopore sequencing. Despite admission to the intensive care unit, the patient died within 48 hrs of admission. CONCLUSIONS: This case demonstrates the need for increased awareness of hypervirulent K. pneumoniae, even in countries where it occurs infrequently. Novel, rapid, sequencing technologies can support diagnosis in unusual presentations.

Synthesis, antimicrobial and chitinase inhibitory activities of 3-amidocoumarins.

A series of 3-amidocoumarins has been synthesized and tested in vitro for their anitimicrobial and chitinase inhibitory activities. Among these, compounds 5k, 5l, 8b-8d, 8f and 8g exhibited good antibacterial activity with MIC values in the range of 6.25-25 µg/mL against some of the tested strains while compounds 5l, 8b, 8c and 8f showed good activity against at least one or two fungal strains. Some of the assayed compounds 5d, 5k, 5l, 8b and 8c displayed significant chitinase inhibitory activity with IC50 values in the range of 3.74-5.6 µM. Among them, 5l proved to be potent chitinase inhibitor with IC50 value of 3.74 µM. To better understand the enzyme-inhibitor interactions molecular docking study of all the synthesized compounds was carried out on Aspergillus fumigatus chitinase 1W9U. The compound 5l showed high binding affinity with the receptor with binding energy value of -8.44 Kcal/mol. This study also provides structure activity relationship (SAR) of synthesized compounds.

Periodontal disease in free-ranging koalas (Phascolarctos cinereus) from the Mount Lofty Ranges, South Australia, and its association with koala retrovirus infection.

BACKGROUND: In northern Australian koala populations (Queensland and New South Wales), periodontal disease (gingivitis and periodontitis) is common while koala retrovirus subtype A is endogenous, with other subtypes transmitted exogenously. Koala retrovirus has been hypothesised to cause immune suppression and may predispose koalas to diseases caused by concurrent infections. In southern Australia populations (Victoria and South Australia) periodontal disease has not been investigated, and koala retrovirus is presumably exogenously transmitted. This study described oral health in South Australian koalas and investigated if an association between periodontal disease and koala retrovirus exists. METHODS: Oral health was examined for wild-caught koalas from the Mount Lofty Ranges (n = 75). Koala retrovirus provirus was detected in whole blood using nested PCR and proviral load determined with qPCR. Periodontal disease severity was recorded and used to calculate the Final Oral Health Index (0-normal, 24-severe).Results Periodontal disease was observed in 84% (63/75) of koalas; 77% had gingivitis (58/75) and 65% (49/75) had periodontitis. The average Final Oral Health Index was 5.47 (s.d 3.13). Most cases of periodontal disease were associated with the incisors. Koala retrovirus-infected koalas were more likely to present with periodontitis (p = 0.042) and the Final Oral Health Index was negatively correlated with proviral load (ρ = -0.353, p = 0.017). CONCLUSION: South Australian koalas had a high prevalence of gingivitis and periodontitis. Periodontal disease was more prevalent in the incisors. Exogenous koala retrovirus infection may also facilitate the development of periodontitis by modulation of the immune response to concurrent oral bacterial infections.

Classical hydrogen bonding and stacking of chelate rings in new copper(ii) complexes.

Three new copper(ii) complexes, viz., [Cu(L)(NO3)(H2O)]H2O 1, [Cu(L)(H2O)2]NO32 and [Cu2(L)2(pyrazine)](ClO4)2·4H2O 3, were prepared using a biomimetic synthesis strategy [HL = 4-chloro-2-{(E)-[2-(pyridin-2-yl)hydrazinylidene]methyl}phenol]. Structural characterization revealed very different local geometries around copper(ii) ions, being square pyramidal for mononuclear complexes (τ5 = 0.021 for 1 and τ5 = 0.13 for 2) and square planar for homobinuclear pyrazine bridged complex 3 (τ4 = 0.06). In complex 3, stacking of chelate rings was observed. This insight was thought to provide new structural evidence for the stacking of the planar chelate rings. These π-interactions provide stability to the crystal structure of homobinuclear complex 3. Magnetic measurements of bulk materials 1, 2 and 3 revealed weak antiferromagnetic coupling in all complexes. The EPR spectra of complexes 1, 2 and 3 in polycrystalline state exhibited broad signals at g ≅ 2.15 owing to spin-spin interactions between two copper ions. The cyclic voltammograms of mononuclear complexes (1 and 2) in DMSO gave one CuII/CuI irreversible wave. On the other hand, pyrazine bridged binuclear complex 3 exhibited two waves, which correspond to CuIICuII/CuIICuI and CuIICuI/CuICuI redox processes. Differential pulse voltammetry (DPV) experiments also exhibited the same reduction behavior. These complexes displayed effective antioxidant SOD activity and exhibit the outlines of a structure-based cyclic mechanism. On the basis of experimental and theoretical DFT studies, the structure-activity relationships of these complexes have also been discussed.

Mass drug administration of azithromycin for trachoma reduces the prevalence of genital Chlamydia trachomatis infection in the Solomon Islands.

OBJECTIVES: Chlamydia trachomatis is the most common bacterial sexually transmitted infection and is frequently asymptomatic; ocular C. trachomatis strains cause trachoma. Mass drug administration (MDA) of azithromycin for trachoma might also reduce the prevalence of genital C. trachomatis. In a survey conducted in the Solomon Islands in 2014, prior to MDA, the prevalence of genital C. trachomatis was 20.3% (95% CI 15.9% to 25.4%). We conducted a survey to establish the impact of MDA with azithromycin on genital C. trachomatis. METHODS: Women attending three community outpatient clinics, predominantly for antenatal care, 10 months after MDA with azithromycin given for trachoma elimination, were enrolled in this survey. Self-taken high vaginal swabs were for C. trachomatis and Neisseria gonorrhoeae using the BD Probetec strand displacement assay. RESULTS: 298 women were enrolled. C. trachomatis infection was diagnosed in 43 women (14.4%, 95% CI 10.6% to 18.9%) and N. gonorrhoeae in 9 (3%, 95% CI 1.4% to 5.7%). The age-adjusted OR for C. trachomatis infection was consistent with a significant decrease in the prevalence of C. trachomatis following MDA (OR 0.58, 95% CI 0.37 to 0.94, p=0.027). There was no change in the prevalence of N. gonorrhoeae between following MDA (OR 0.51, 95% CI 0.22 to 1.22, p=0.13). CONCLUSIONS: This study demonstrated a 40% reduction in the age-adjusted prevalence of genital C. trachomatis infection following azithromycin MDA for trachoma elimination.

Prevalence of sexually transmitted infections in female clinic attendees in Honiara, Solomon Islands.

OBJECTIVES: This study sought to determine the prevalence of common bacterial sexually transmitted infections, including Chlamydia trachomatis and Neisseria gonorrhoeae, in women attending clinics in the Solomon Islands. METHODS: We conducted a sexual health survey among women attending three nurse-led community outpatient clinics in August 2014, to establish the prevalence of bacterial sexually transmitted infections in female clinic attenders in Honiara, Solomon Islands. Vaginal swab samples were tested for infection with C. trachomatis and N. gonorrhoeae using a commercial strand displacement amplification assay. Serum samples were tested for syphilis. RESULTS: We enrolled 296 women, aged 16-49, attending three clinics. Knowledge of safe sexual practices was high but reported condom usage was low. The prevalence of infection with C. trachomatis was 20%. The prevalence of infection with N. gonorrhoeae and syphilis were 5.1% and 4.1%, respectively. CONCLUSIONS: Bacterial sexually transmitted infections are a major health problem in the Solomon Islands. Interventions are urgently needed.

1,3,5-Tri-p-tolyl-pentane-1,5-diol.

In the title compound, C26H30O2, the central benzene ring forms dihedral angles of 14.85 (15) and 28.17 (14)° with the terminal benzene rings. The dihedral angle between the terminal benzene rings is 32.14 (13)°. The crystal packing exhibits two strong inter-molecular O-H⋯O hydrogen bonds, forming directed four-membered co-operative rings. A region of disordered electron density, most probably disordered ethyl acetate solvent mol-ecules, occupying voids of ca 519 Å(3) for an electron count of 59, was treated using the SQUEEZE routine in PLATON [Spek (2009 ▶). Acta Cryst. D65, 148-155]. Their formula mass and unit-cell characteristics were not taken into account during refinement. The structure was refined as an inversion twin [absolute structure parameter = -0.3 (4)].

2-(Naphthalen-1-yl)-1-phenyl-1H-benzimid-azole benzene hemisolvate.

In the title compound, C23H16N2·0.5C6H6, the benzimidazole unit [maximum deviation = 0.0258 (6) Å] and the naphthalene ring system [maximum deviation = 0.0254 (6) Å] are both essentially planar and make a dihedral angle of 61.955 (17)°. The imidazole ring makes dihedral angle of 61.73 (4)° with the phenyl ring. An intra-molecular C-H⋯N hydrogen bond generates an S(6) ring motif. In the crystal, seven weak C-H⋯π inter-actions involving the fused ring system, the benzene solvent mol-ecule, the imidazole phenyl rings are observed, leading to a three-dimensional architecture.

1,5-Bis(4-chloro-phen-yl)-3-(4-methyl-phen-yl)pentane-1,5-dione.

In the title mol-ecule, C24H20Cl2O2, the central methyl-benzene ring forms dihedral angles of 42.47 (10) and 34.34 (10)° with the terminal 4-chloro-phenyl fragments. The dihedral angle between the chloro-benzene rings is 34.45 (11)°. A weak intra-molecular C-H⋯O inter-action generates an S(6) ring motif. The crystal packing exhibits weak C-H⋯O hydrogen bonds and C-H⋯π inter-actions.

10-Methyl-2-oxo-4-phenyl-2,11-di-hydro-pyrano[2,3-a]carbazole-3-carbo-nitrile.

In the title mol-ecule, C23H14N2O2, the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1018 (8) Å]. The pyrrole ring makes dihedral angles of 4.44 (5), 3.84 (5), 2.18 (5) and 56.44 (5)° with the pyran, fused benzene rings and phenyl ring, respectively. In the crystal, pairs of N-H⋯O hydrogen bonds generate R 2 (2)(14) loops and a C-H⋯N inter-action is also found. Mol-ecules are further linked by a number of π-π interactions [centroid-centroid distances vary from 3.5702 (5) to 3.7068 (6) Å], forming a three-dimensional network.

Microwave-assisted synthesis and spasmolytic activity of 4-indolylhexahydroquinoline derivatives.

In the present study a microwave-assisted one-pot method was applied for the synthesis of 18 novel condensed 1,4-dihydropyridines carrying the indole moiety. The compounds were achieved by the reaction of appropriate 1,3-cyclohexanedione, substituted indole carboxaldehyde derivative, alkyl acetoacetate and ammonium acetate in methanol, according to a modified Hantzsch reaction. The structure elucidation of the compounds was carried out by spectral methods including X-ray studies. Their spasmolytic activities through calcium channel blockade were assayed on isolated rat ileum. The obtained results indicated that the introduction of the brom atom on the indole ring altered the mentioned activity positively.

7-Methyl-1-phenyl-1,10-di-hydro-pyrazolo-[3,4-a]carbazole.

In the title mol-ecule, C20H15N3, the atoms in the carbazole unit deviate from planarity [maximum deviation from mean plane = 0.1082 (15) Å]. The pyrrole ring makes dihedral angles of 3.17 (8)/4.10 (9), 7.20 (9) and 44.62 (9)° with the fused benzene, pyrazole and phenyl rings, respectively. In the crystal, mol-ecules are linked via N-H⋯N hydrogen bonds, forming an infinite chain along [010]. Mol-ecules are further linked by nine π-π [centroid-centroid distances vary from 3.6864 (11) to 3.9802 (11) Å] and one C-H⋯π inter-action, forming a three-dimensional network.

Impact of pharyngeal closure technique on fistula after salvage laryngectomy.

IMPORTANCE: No consensus exists as to the best technique, or techniques, to optimize wound healing, decrease pharyngocutaneous fistula formation, and shorten both hospital length of stay and time to initiation of oral intake after salvage laryngectomy. We sought to combine the recent experience of multiple high-volume institutions, with different reconstructive preferences, in the management of pharyngeal closure technique for post-radiation therapy salvage total laryngectomy in an effort to bring clarity to this clinical challenge. OBJECTIVE: To determine if the use of vascularized flaps in either an onlay or interposed fashion reduces the incidence or duration of pharyngocutaneous fistula after salvage laryngectomy compared with simple primary closure of the pharynx. DESIGN: Multi-institutional retrospective review of all patients undergoing total laryngectomy after having received definitive radiation therapy with or without chemotherapy between January 2005 and January 2012, conducted at 7 academic medical centers. SETTING: Academic, tertiary referral centers. PATIENTS: The study population comprised 359 patients from 8 institutions. All patients had a history of laryngeal irradiation and underwent laryngectomy between 2005 and 2012. They were grouped as primary closure, pectoralis myofascial onlay flap, or interposed free tissue. All patients had a minimum of 4 months follow-up. MAIN OUTCOMES AND MEASURES: Fistula incidence, severity, and predictors of fistula. RESULTS: Of the 359 patients, fistula occurred in 94 (27%). For patients with fistula, hospital stay increased from 8.9 to 12.1 days (P < .001) and oral diet initiation was delayed from 10.5 days to 29.9 days (P < .001). Patients were grouped according to closure technique: primary closure (n = 99), pectoralis onlay flap (n = 40), and interposed free tissue (n = 220). Incidence of fistula with primary closure was 34%. For the interposed free flap group, the fistula rate was lower at 25% (P = .07). Incidence of fistula was the lowest for the pectoralis onlay group at 15% (P = .02). Multivariate analysis confirmed a significantly lower fistula rate with either flap technique. For patients who developed fistula, mean duration of fistula was significantly prolonged with primary closure (14.0 weeks) compared with pectoralis flap (9.0 weeks) and free flap (6.5 weeks). CONCLUSIONS AND RELEVANCE: Pharyngocutaneous fistula remains a significant problem following salvage laryngectomy. Use of nonirradiated, vascularized flaps reduced the incidence and duration of fistula and should be considered during salvage laryngectomy.

2-(1-Phenyl-1H-benzimidazol-2-yl)phenol.

In the title mol-ecule, C19H14N2O, the benzimidazole unit is close to being planar [maximum deviation = 0.0253 (11) Å] and forms dihedral angles of 68.98 (6) and 20.38 (7)° with the adjacent phenyl and benzene rings; the dihedral angle between the latter two planes is 64.30 (7)°. An intra-molecular O-H⋯N hydrogen bond generates an S(6) ring motif. In the crystal, mol-ecules are linked by C-H⋯N and C-H⋯O hydrogen bonds, and consolidated into a three-dimensional architecture by π-π stacking inter-actions, with a centroid-centroid distance of 3.8428 (12) Å.