Epidemiological and entomological evaluations after six years or more of mass drug administration for lymphatic filariasis elimination in Nigeria

The current strategy for interrupting transmission of lymphatic filariasis (LF) is annual mass drug administration (MDA), at good coverage, for 6 or more years. We describe our programmatic experience delivering the MDA combination of ivermectin and albendazole in Plateau and Nasarawa states in central Nigeria, where LF is caused by anopheline transmitted Wuchereria bancrofti. Baseline LF mapping using rapid blood antigen detection tests showed mean local government area (LGA) prevalence of 23% (range 4-62%). MDA was launched in 2000 and by 2003 had been scaled up to full geographic coverage in all 30 LGAs in the two states; over 26 million cumulative directly observed treatments were provided by community drug distributors over the intervention period. Reported treatment coverage for each round was ≥85% of the treatment eligible population of 3.7 million, although a population-based coverage survey in 2003 showed lower coverage (72.2%; 95% CI 65.5-79.0%). To determine impact on transmission, we monitored three LF infection parameters (microfilaremia, antigenemia, and mosquito infection) in 10 sentinel villages (SVs) serially. The last monitoring was done in 2009, when SVs had been treated for 7-10 years. Microfilaremia in 2009 decreased by 83% from baseline (from 4.9% to 0.8%); antigenemia by 67% (from 21.6% to 7.2%); mosquito infection rate (all larval stages) by 86% (from 3.1% to 0.4%); and mosquito infectivity rate (L3 stages) by 76% (from 1.3% to 0.3%). All changes were statistically significant. Results suggest that LF transmission has been interrupted in 5 of the 10 SVs, based on 2009 finding of microfilaremia ≥1% and/or L3 stages in mosquitoes. Four of the five SVs where transmission persists had baseline antigenemia prevalence of >25%. Longer or additional interventions (e.g., more frequent MDA treatments, insecticidal bed nets) should be considered for 'hot spots' where transmission is ongoing.     

Skin extracellular matrix components accelerate the regenerative potential of Lin− cells

Due to their unique properties, bone marrow-derived Lin^? cells can be used to regenerate damaged tissues, including skin. The objective of our study was to determine the influence of the skin tissue-specific microenvironment on mouse Lin^? cell proliferation and migration in vitro. Cells were analyzed for the expression of stem/progenitor surface markers by flow cytometry. Proliferation of MACS-purified cells in 3D cultures was investigated by WST-8 assay. Lin^? cell migration was evaluated by in vitro scratch assay. The results obtained show that basement membrane matrix is more effective for Lin^? cell proliferation in vitro. However, type I collagen matrix better enhances the re-epithelization process, that depends on the cell migratory properties. These studies are important for preparing cells to be used in transplantation.     

Status of Onchocerciasis Transmission after More Than a Decade of Mass Drug Administration for Onchocerciasis and Lymphatic Filariasis Elimination in Central Nigeria: Challenges in Coordinating the Stop MDA Decision

Background

This study was undertaken in five onchocerciasis/lymphatic filariasis (LF) co-endemic local government areas (LGAs) in Plateau and Nasarawa, Nigeria. Annual MDA with ivermectin had been given for 17 years, 8 of which were in combination with albendazole. In 2008, assessments indicated that LF transmission was interrupted, but that the MDA had to continue due to the uncertain status of onchocerciasis transmission. Accordingly, assessments to determine if ivermectin MDA for onchocerciasis could be stopped were conducted in 2009.

Methods

We evaluated nodule, microfilarial (mf) skin snip, and antibody (IgG4 response to OV16) prevalence in adults and children in six sentinel sites where baseline data from the 1990s were available. We applied the 2001 WHO criteria for elimination of onchocerciasis that defined transmission interruption as an infection rate of <0.1% in children (using both skin snip and OV16 antibody) and a rate of infective (L3) blackflies of <0.05%.

Results

Among adult residents in sentinel sites, mean mf prevalence decreased by 99.37% from the 1991–1993 baseline of 42.95% (64/149) to 0.27% (2/739) in 2009 (p<0.001). The OV16 seropositivity of 3.52% (26/739) among this same group was over ten times the mf rate. No mf or nodules were detected in 4,451 children in sentinel sites and ‘spot check’ villages, allowing the exclusion of 0.1% infection rate with 95% confidence. Seven OV16 seropositives were detected, yielding a seroprevalence of 0.16% (0.32% upper 95%CI). No infections were detected in PCR testing of 1,568 Simulium damnosum s.l. flies obtained from capture sites around the six sentinel sites.

Conclusion

Interruption of transmission of onchocerciasis in these five LGAs is highly likely, although the number of flies caught was insufficient to exclude 0.05% with 95% confidence (upper CI 0.23%). We suggest that ivermectin MDA could be stopped in these LGAs if similar results are seen in neighboring districts.     

Development and validation of a chiral LC-MS method for the enantiomeric resolution of (+) and (−)-medetomidine in equine plasma by using polysaccharide-based chiral stationary phases

The detection and separation of medetomidine enantiomers from the complex biological matrices poses a great analytical challenge, especially in the field of forensic toxicology and pharmacology. Couple of researchers reported resolution of medetomidine using protein-based chiral columns, but the reported method is quiet challenging and tedious to be employed for routine analysis. This research paper reported a method that enables the enantio-separation of medetomidine by using polysaccharide cellulose chiral column. The use of chiralcel OJ-3R column was found to have the highest potential for successful chiral resolution. Ammonium hydrogen carbonate was the ideal buffer salt for chiral liquid chromatography (LC) with electrospray ionization (ESI)+ mass spectrometry (MS) detection for the successful separation and detection of racemic compound. The method was linear over the range of 0 to 20 ng/mL in equine plasma and the inter-day precisions of levomedetomidine, dexmedetomidine were 1.36% and 1.89%, respectively. The accuracy of levomedetomidine was in the range of 99.25% to 101.57% and that for dexmedetomidine was 99.17% to 100.99%. The limits of quantification for both isomers were 0.2 ng/mL. Recovery and matrix effect on the analytes were also evaluated. Under the optimized conditions, the validated method can be adapted for the identification and resolution of the medetomidine enantiomers in different matrices used for drug testing and analysis.     

Attitudes and sexual behaviours of unmarried people with HIV/AIDS living in the Niger Delta region of Nigeria

Background Increasing morbidity and mortality associated with HIV/AIDS may be attributable to the lifestyle of individuals. Appropriate sexual behaviour and lifestyle modification may be helpful strategies for prevention and control of HIV/AIDS in many countries.Aim The study was designed to assess the impact of attitudes and sexual behaviour on control of HIV/AIDS among unmarried people living with HIV/AIDS in Uyo, a community in the Niger Delta region of Nigeria.Method A total of 365 unmarried individuals living with HIV/AIDS were assessed at the HIV clinic of the University of Uyo Teaching Hospital. Attitudes and sexual behaviour were evaluated using the Attitude and Sexual Behaviour Questionnaire adapted from previous studies.Results Of the 365 individuals living with HIV/AIDS, 142 (38.9%) were male and 223 (61.1%) were female. The majority of the subjects were below 50 years of age. The mean ages (± SD) of men and women were 36.8 ± 3.9 and 29.2 ± 1.7 years, respectively. Sexual attitudes and behaviours were variable. There was no change in the partner''s reaction to sex for 28.9% of men and 27.8% of women, abstinence in 7.7% of men and 8.1% of women, and breakdown of the relationship with the partner for 4.9% of men and 7.2% of women. More women than men agreed to undergo testing after their partners had tested positive for HIV. Sexual activity was higher in women than men, with 4.9% of men and 10.3% of women reporting daily sexual intercourse, 16.2% of men and 15.7% of women reporting weekly intercourse, and occasional sexual intercourse being reported by 44.4% of both men and women. After testing positive, 58.4% of male partners and 56.9% of female partners were persuaded to use condoms during sexual intercourse.Conclusion This study has demonstrated unhealthy attitudes and sexual behaviour among individuals living with HIV/AIDS in the Niger Delta region of Nigeria. This can potentially limit efforts and investment in controlling HIV/AIDS in this region. Therefore there is a need to initiate concrete policies and programmes that would encourage people living with HIV/AIDS in the Niger Delta region to adopt a healthy lifestyle.     

Parp1–XRCC1 and the repair of DNA double strand breaks in mouse round spermatids

The repair of DNA double strand breaks (DSBs) in male germ cells is slower and differently regulated compared to that in somatic cells. Round spermatids show DSB repair and are radioresistant to apoptosis induction. Mutation induction studies using ionizing irradiation, indicated a high frequency of chromosome aberrations (CA) in the next generation. Since they are in a G1 comparable stage of the cell cycle, haploid spermatids are expected to repair DSBs by the non-homologous end-joining pathway (NHEJ). However, immunohistochemical evidence indicates that not all components of the classical NHEJ pathway are available since the presence of DNA-PKcs cannot be shown. Here, we demonstrate that round spermatids, as well as most other types of male germ cells express both Parp1 and XRCC1. Therefore, we have determined whether the alternative Parp1/XRCC1 dependent NHEJ pathway is active in these nuclei and also have tested for classical NHEJ activity by a genetic method. To evaluate DSB repair in SCID mice, deficient for DNA-PKcs, and to study the involvement of the Parp1/XRCC1 dependent NHEJ pathway in round spermatids, the loss of γ-H2AX foci after irradiation has been determined in nucleus spreads of round spermatids of SCID mice and in nucleus spreads and histological sections of Parp1-inhibited mice and their respective controls. Results show that around half of the breaks in randomly selected round spermatids are repaired between 1 and 8 h after irradiation. The repair of 16% of the induced DSBs requires DNA-PKcs and 21% Parp1. Foci numbers in the Parp1-inhibited testes tend to be higher in spermatids of all epithelial stages reaching significance in stages I–III which indicates an active Parp1/XRCC1 pathway in round spermatids and a decreased repair capacity in later round spermatid stages. In Parp1-inhibited SCID mice only 14.5% of the breaks were repaired 8 h after irradiation indicating additivity of the two NHEJ pathways in round spermatids.     

Mass ivermectin treatment for Onchocerciasis: Lack of evidence for collateral impact on transmission of Wuchereria bancrofti in areas of co-endemicity

There has long been interest in determining if mass ivermectin administration for onchocerciasis has 'unknowingly' interrupted lymphatic filariasis (LF) transmission where the endemicity of the two diseases' overlaps. We studied 11 communities in central Nigeria entomologically for LF by performing mosquito dissections on Anopheline LF vectors. Six of the communities studied were located within an onchocerciasis treatment zone, and five were located outside of that zone. Communities inside the treatment zone had been offered ivermectin treatment for two-five years, with a mean coverage of 81% of the eligible population (range 58–95%). We found 4.9% of mosquitoes were infected with any larval stage of W. bancrofti in the head or thorax in 362 dissections in the untreated villages compared to 4.7% infected in 549 dissections in the ivermectin treated villages (Mantel-Haenszel ChiSquare 0.02, P = 0.9). We concluded that ivermectin annual therapy for onchocerciasis has not interrupted transmission of Wuchereria bancrofti (the causative agent of LF in Nigeria).     

Dwarf plants of diploid <Emphasis Type="Italic">Medicago sativa</Emphasis> carry a mutation in the gibberellin 3-β-hydroxylase gene

In this paper we describe the identification of a gene, MsDWF1 coding for a putative gibberellin 3-beta-hydroxylase (GA3ox), whose natural mutation is conditioning a dwarf growth phenotype in Medicago sativa. The dwarf phenotype could not be complemented with grafting, which indicates that the bioactive gibberellin compound necessary for shoot elongation is immobile. On the contrary, exogenously added gibberellic acid restored normal growth. The genetic position of the Msdwf1 gene was mapped to linkage group 2 (LG2) and the physical location was delimited by map-based cloning using Medicago truncatula genomic resources. Based on the similar appearance and behavior of the dwarf Medicago sativa plants to the pea stem length mutant (le) as well as the synthenic map position of the two genes it was postulated that MsDWF1 and pea Le are orthologs. The comparison of wild type and mutant allele sequences of MsGA3ox revealed an amino acid change in a conserved position in the mutant allele, which most probably impaired the function of the enzyme. Our results indicate that the dwarf phenotype was the consequence of this mutation.     

Synthesis and bioactivity of several new hetaryl sulfonamides

1-(4-Methylsulfonyl)-2-thione-4-aryl-5-Z-6-methyl and oxyalkyl-imidazoles were synthesized from different tetrahydropyrimidinethiones and aryl sulfonyl chloride. These compunds were tested for metal chelating effects and to determine the phrase in which inhibition occured between two physiologically pertinent compunds and carbonic anhydrase (CA) isozymes I and II (hCA I and II), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE). AChE was detected in high concentrations in the brain and red blood cells. BChE is another enzymes that is abundant available in the liver and released into the blood in a soluble form. Newly synthesized hetaryl sulfonamides exhibited impressive inhibition profiles with Ki values in the range of 1.42–6.58?nM against hCA I, 1.72–7.41?nM against hCA II, 0.20–1.14?nM against AChE and 1.55–5.92?nM against BChE. Moreover, acetazolamide showed Ki values of 43.69?±?6.44?nM against hCA I and 31.67?±?8.39?nM against hCA II. Additionally, tacrine showed Ki values of 25.75?±?3.39?nM and 37.82?±?2.08 against AChE and BChE, respectively.