Search results for: Cervical Dysplasia
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 243

Search results for: Cervical Dysplasia

3 Benzenepropanamine Analogues as Non-detergent Microbicidal Spermicide for Effective Pre-exposure Prophylaxis

Authors: Veenu Bala, Yashpal S. Chhonker, Bhavana Kushwaha, Rabi S. Bhatta, Gopal Gupta, Vishnu L. Sharma

Abstract:

According to UNAIDS 2013 estimate nearly 52% of all individuals living with HIV are now women of reproductive age (15–44 years). Seventy-five percent cases of HIV acquisition are through heterosexual contacts and sexually transmitted infections (STIs), attributable to unsafe sexual behaviour. Each year, an estimated 500 million people acquire atleast one of four STIs: chlamydia, gonorrhoea, syphilis and trichomoniasis. Trichomonas vaginalis (TV) is exclusively sexually transmitted in adults, accounting for 30% of STI cases and associated with pelvic inflammatory disease (PID), vaginitis and pregnancy complications in women. TV infection resulted in impaired vaginal milieu, eventually favoring HIV transmission. In the absence of an effective prophylactic HIV vaccine, prevention of new infections has become a priority. It was thought worthwhile to integrate HIV prevention and reproductive health services including unintended pregnancy protection for women as both are related with unprotected sex. Initially, nonoxynol-9 (N-9) had been proposed as a spermicidal agent with microbicidal activity but on the contrary it increased HIV susceptibility due to surfactant action. Thus, to accomplish an urgent need of novel woman controlled non-detergent microbicidal spermicides benzenepropanamine analogues have been synthesized. At first, five benzenepropanamine-dithiocarbamate hybrids have been synthesized and evaluated for their spermicidal, anti-Trichomonas and anti-fungal activities along with safety profiling to cervicovaginal cells. In order to further enhance the scope of above study benzenepropanamine was hybridized with thiourea as to introduce anti-HIV potential. The synthesized hybrid molecules were evaluated for their reverse transcriptase (RT) inhibition, spermicidal, anti-Trichomonas and antimicrobial activities as well as their safety against vaginal flora and cervical cells. simulated vaginal fluid (SVF) stability and pharmacokinetics of most potent compound versus N-9 was examined in female Newzealand (NZ) rabbits to observe its absorption into systemic circulation and subsequent exposure in blood plasma through vaginal wall. The study resulted in the most promising compound N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) exhibiting better activity profile than N-9 as it showed RT inhibition (72.30 %), anti-Trichomonas (MIC, 46.72 µM against MTZ susceptible and MIC, 187.68 µM against resistant strain), spermicidal (MEC, 0.01%) and antifungal activity (MIC, 3.12–50 µg/mL) against four fungal strains. The high safety against vaginal epithelium (HeLa cells) and compatibility with vaginal flora (lactobacillus), SVF stability and least vaginal absorption supported its suitability for topical vaginal application. Docking study was performed to gain an insight into the binding mode and interactions of the most promising compound, N-butyl-4-(3-oxo-3-phenylpropyl) piperazin-1-carbothioamide (29) with HIV-1 Reverse Transcriptase. The docking study has revealed that compound (29) interacted with HIV-1 RT similar to standard drug Nevirapine. It may be concluded that hybridization of benzenepropanamine and thiourea moiety resulted into novel lead with multiple activities including RT inhibition. A further lead optimization may result into effective vaginal microbicides having spermicidal, anti-Trichomonas, antifungal and anti-HIV potential altogether with enhanced safety to cervico-vaginal cells in comparison to Nonoxynol-9.

Keywords: microbicidal, nonoxynol-9, reverse transcriptase, spermicide

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2 Hanta Virus Infection in a Child and Sequelae

Authors: Vijay Samuel, Tina Thekkekkara, Shoma Ganguly

Abstract:

There is no reported Hanta Seoul virus infection in children in the UK so far, making it quite challenging for clinicians in diagnosing, predicting and prognosticating the outcome of the infection to patients and parents. We report a case of a ten-year-old girl who presented with pyrexia associated with headache, photophobia and abdominal pain. The family had recently acquired two pet rats six weeks ago. She appeared flushed with peri-oral pallor, coated the strawberry tongue, inflamed tonsils and bilateral cervical lymphadenopathy. Her liver and splenic edges were palpable. Investigations showed that she was thrombocytopenic with deranged renal and liver functions. An ultrasound abdomen demonstrated a mildly enlarged spleen, peripancreatic lymph node and an acalculous cholecystitis. In view of her clinical presentation, a diagnosis of leptospirosis was considered and she was commenced on intravenous benzylpenicillin. The following day she became oliguric, developed significant proteinuria and her renal function deteriorated. Following conservative management, her urine output gradually improved along with her renal function, proteinuria and thrombocytopaenia. Serology for leptospirosis and various other viruses were negative. Following discussion with the Rare and Imported Pathogens Laboratory at Porton hanta virus serology was requested and found to be strongly positive for Seoul hanta virus. Following discharge she developed palpitations, fatigue, severe headache and cognitive difficulties including memory loss and difficulties in spelling, reading and mathematics. Extensive investigations including ECG, MRI brain and CSF studies were performed and revealed no significant abnormalities. Since 2012, there have been six cases of acute kidney injury due to Hantavirus infection in the UK. Two cases were from the Humber region and were exposure to wild rats and the other four were exposed to specially bred pet fancy rats. Hanta virus infections can cause mild flu like symptoms but two clinical syndromes are associated with severe disease including haemorrhagic fever with renal syndrome, which may be associated with thrombocytopenia and Hantavirus cardiopulmonary syndrome. Neuropsychological impairments reported following hantavirus pulmonary syndrome and following Puumala virus infection have been reported. Minor white matter lesions were found in about half of the patients investigated with MRI brain. Seoul virus has a global distribution owing to the dispersal of its carrier host rats, through global trade. Several ports in the region could explain the possible establishment of Seoul virus in local populations of rats in the Yorkshire and Humber region. The risk of infection for occupationally exposed groups is 1-3% compared to 32.9% for specialist pet rat owners. The report highlight’s the importance of routinely asking about pets in the family. We hope to raise awareness of the emergence of hantavirus infection in the UK, particularly in the Yorkshire and Humber region. Clinicians should consider hantavirus infection as a potential cause of febrile illness causing renal impairment in children. Awareness of the possible neuro-cognitive sequele would help the clinicians offer appropriate information and support to children and their families. Contacting Rare and Imported Pathogens Laboratory at Porton is a useful resource for clinicians in UK when they consider unusual infections.

Keywords: Seoul hantavirus in child Porton, UK Acute kidney injury

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1 Improving Data Completeness and Timely Reporting: A Joint Collaborative Effort between Partners in Health and Ministry of Health in Remote Areas, Neno District, Malawi

Authors: Wiseman Emmanuel Nkhomah, Chiyembekezo Kachimanga, Moses Banda Aron, Julia Higgins, Manuel Mulwafu, Kondwani Mpinga, Mwayi Chunga, Grace Momba, Enock Ndarama, Dickson Sumphi, Atupere Phiri, Fabien Munyaneza

Abstract:

Background: Data is key to supporting health service delivery as stakeholders, including NGOs rely on it for effective service delivery, decision-making, and system strengthening. Several studies generated debate on data quality from national health management information systems (HMIS) in sub-Saharan Africa. This limits the utilization of data in resource-limited settings, which already struggle to meet standards set by the World Health Organization (WHO). We aimed to evaluate data quality improvement of Neno district HMIS over a 4-year period (2018 – 2021) following quarterly data reviews introduced in January 2020 by the district health management team and Partners In Health. Methods: Exploratory Mixed Research was used to examine report rates, followed by in-depth interviews using Key Informant Interviews (KIIs) and Focus Group Discussions (FGDs). We used the WHO module desk review to assess the quality of HMIS data in the Neno district captured from 2018 to 2021. The metrics assessed included the completeness and timeliness of 34 reports. Completeness was measured as a percentage of non-missing reports. Timeliness was measured as the span between data inputs and expected outputs meeting needs. We computed T-Test and recorded P-values, summaries, and percentage changes using R and Excel 2016. We analyzed demographics for key informant interviews in Power BI. We developed themes from 7 FGDs and 11 KIIs using Dedoose software, from which we picked perceptions of healthcare workers, interventions implemented, and improvement suggestions. The study was reviewed and approved by Malawi National Health Science Research Committee (IRB: 22/02/2866). Results: Overall, the average reporting completeness rate was 83.4% (before) and 98.1% (after), while timeliness was 68.1% and 76.4 respectively. Completeness of reports increased over time: 2018, 78.8%; 2019, 88%; 2020, 96.3% and 2021, 99.9% (p< 0.004). The trend for timeliness has been declining except in 2021, where it improved: 2018, 68.4%; 2019, 68.3%; 2020, 67.1% and 2021, 81% (p< 0.279). Comparing 2021 reporting rates to the mean of three preceding years, both completeness increased from 88% to 99% (in 2021), while timeliness increased from 68% to 81%. Sixty-five percent of reports have maintained meeting a national standard of 90%+ in completeness while only 24% in timeliness. Thirty-two percent of reports met the national standard. Only 9% improved on both completeness and timeliness, and these are; cervical cancer, nutrition care support and treatment, and youth-friendly health services reports. 50% of reports did not improve to standard in timeliness, and only one did not in completeness. On the other hand, factors associated with improvement included improved communications and reminders using internal communication, data quality assessments, checks, and reviews. Decentralizing data entry at the facility level was suggested to improve timeliness. Conclusion: Findings suggest that data quality in HMIS for the district has improved following collaborative efforts. We recommend maintaining such initiatives to identify remaining quality gaps and that results be shared publicly to support increased use of data. These results can inform Ministry of Health and its partners on some interventions and advise initiatives for improving its quality.

Keywords: data quality, data utilization, HMIS, collaboration, completeness, timeliness, decision-making

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