Mother Kevin Postgraduate Medical School

Permanent URI for this communityhttp://hdl.handle.net/20.500.12280/169

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Doxycycline for the Treatment of Nodding Syndrome (DONS); The Study Protocol of a Phase II Randomised Controlled Trial
(Springer Nature, 2019-03-06) Idro, Richard; Anguzu, Ronald; Ogwang, Rodney; Akun, Pamela; Abbo, Catherine; Mwaka, Amos Deogratius; Opar, Bernard; Nakamya, Phyellister; Taylor, Mark; Elliott, Alison; Vincent, Angela; Newton, Charles; Marsh, Kevin
Background Nodding syndrome is a poorly understood neurological disorder of unknown aetiology, affecting several thousand children in Africa. There has been a consistent epidemiological association with infection by the filarial parasite, Onchocerca volvulus and antibodies to leiomodin and DJ-1, cross-reacting with O.volvulus proteins, have been reported. We hypothesized that nodding syndrome is a neuro-inflammatory disorder, induced by antibodies to O.volvulus or its symbiont, Wolbachia, cross-reacting with human neuron proteins and that doxycycline, which kills Onchocerca through effects on Wolbachia, may be used as treatment. Methods This will be a two-arm, double-blind, placebo-controlled, randomised phase II trial of doxycycline 100 mg daily for six weeks in 230 participants. Participants will be patients’ ages≥8 years with nodding syndrome. They will receive standard of care supportive treatment. All will be hospitalised for 1–2 weeks during which time baseline measurements including clinical assessments, EEG, cognitive and laboratory testing will be performed and antiepileptic drug doses rationalised. Participants will then be randomised to either oral doxycycline (Azudox®, Kampala Pharmaceutical Industries) 100 mg daily or placebo. Treatment will be initiated in hospital and continued at home. Participants will be visited at home at 2, 4 and 6 weeks for adherence monitoring. Study outcomes will be assessed at 6, 12, 18 and 24-month visits. Analysis will be by intention to treat. The primary efficacy outcome measure will be the proportion of patients testing positive and the levels or titires of antibodies to host neuron proteins (HNPs) and/or leiomodin at 24 months. Secondary outcome measures will include effect of the intervention on seizure control, inflammatory markers, cognitive function, disease severity and quality of life. Discussion This trial postulates that targeting O.volvulus through drugs which kill Wolbachia can modify the pathogenic processes in nodding syndrome and improve outcomes. Findings from this study are expected to substantially improve the understanding and treatment of nodding syndrome.
Household Poverty, Schooling, Stigma and Quality of Life in Adolescents With Epilepsy in Rural Uganda
(Elsevier, 2020-11-25) Anguzu, Ronald; Akun, Pamela; Katairo, Thomas; Abbo, Catherine; Ningwa, Albert; Ogwang, Rodney; Mwaka, Amos Deogratius; Marsh, Kevin; Newton, R. Charles; Idro, Richard
Background Epilepsy remains a leading chronic neurological disorder in Low- and Middle-Income Countries. In Uganda, the highest burden is among young rural people. We aimed to; (i) describe socio-economic status (including schooling), and household poverty in adolescents living with epilepsy (ALE) compared to unaffected counterparts in the same communities and (ii) determine the factors associated with the overall quality of life (QoL). Methods This was a cross-sectional survey nested within a larger study of ALE compared to age matched healthy community children in Uganda. Between Sept 2016 to Sept 2017, 154 ALE and 154 healthy community controls were consecutively recruited. Adolescents recruited were frequency and age-matched based on age categories 10–14 and 15–19 years. Clinical history and standardized assessments were conducted. One control participant had incomplete assessment and was excluded. The primary outcome was overall QoL and key variables assessed were schooling status and household poverty. Descriptive and multivariable linear regression analysis were conducted for independent associations with overall QoL. Results Mean (SD) age at seizure onset was 8.8 (3.9) years and median (IQR) monthly seizure burden was 2 (1–4). Epilepsy was associated with living in homes with high household poverty; 95/154 (61.7%) ALE lived in the poorest homes compared to 68/153 (44.5%) of the healthy adolescents, p = 0.001. Nearly two-thirds of ALE had dropped out of school and only 48/154 (31.2%) were currently attending school compared to 136/153 (88.9%) of healthy controls, p < 0.001. QoL was lowest among ALE who never attended school (p < 0.001), with primary education (p = 0.006) compared to those with at least secondary education. Stigma scores [mean(SD)] were highest among ALE in the poorest [69.1(34.6)], and wealthy [70.2(32.2)] quintiles compared to their counterparts in poorer [61.8(31.7)], medium [68.0(32.7)] and wealthiest [61.5(33.3)] quintiles, though not statistically significant (p = 0.75). After adjusting for covariates, ALE currently attending school had higher overall QoL compared to their counterparts who never attended school (β = 4.20, 95%CI: 0.90,7.49, p = 0.013). QoL scores were higher among ALE with ≥secondary education than those with no or primary education (β = 10.69, 95%CI: 1.65, 19.72). Conclusions ALE in this rural area are from the poorest households, are more likely to drop out of school and have the lowest QoL. Those with poorer seizure control are most affected. ALE should be included among vulnerable population groups and in addition to schooling, strategies for seizure control and addressing the epilepsy treatment gap in affected homes should be specifically targeted in state poverty eradication programs
Is Nodding Syndrome an Onchocerca Volvulus-Induced Neuroinflammatory Disorder? Uganda’s Story of Research in Understanding the Disease
(Elsevier, 2016-04) Idro, Richard; Opar, Bernard; Wamala, Joseph; Abbo, Catherine; Onzivua, Sylvester; Mwaka, Amos Deogratius; Kakooza-Mwesige, Angelina; Mbonye, Anthony; Aceng, Ruth Jane
Nodding syndrome is a devastating neurological disorder, mostly affecting children in eastern Africa. An estimated 10 000 children are affected. Uganda, one of the most affected countries, set out to systematically investigate the disease and develop interventions for it. On December 21, 2015, the Ministry of Health held a meeting with community leaders from the affected areas to disseminate the results of the investigations made to date. This article summarizes the presentation and shares the story of studies into this peculiar disease. It also shares the results of preliminary studies on its pathogenesis and puts into perspective an upcoming treatment intervention. Clinical and electrophysiological studies have demonstrated nodding syndrome to be a complex epilepsy disorder. A definitive aetiological agent has not been established, but in agreement with other affected countries, a consistent epidemiological association has been demonstrated with infection by Onchocerca volvulus. Preliminary studies of its pathogenesis suggest that nodding syndrome may be a neuroinflammatory disorder, possibly induced by antibodies to O. volvulus cross-reacting with neuron proteins. Histological examination of post mortem brains has shown some yet to be characterized polarizable material in the majority of specimens. Studies to confirm these observations and a clinical trial are planned for 2016.
Is the Glass Half Full or Half Empty? A Qualitative Exploration on Treatment Practices and Perceived Barriers to Biomedical Care for Patients With Nodding Syndrome in Post-Conflict Northern Uganda
(BioMed Central Ltd, 2015-08-29) Mwaka, Amos Deogratius; Okello, S. Elialilia; Abbo, Catherine; Odwong, Okot Francis; Olango, Willy; Etolu, Wilson John; Oriyabuzu, Rachel; Kitara, Lagoro David; Mutamba, Brian Byamah; Idro, Richard; Opar, Toliva Bernard; Aceng, Ruth Jane; Lukwago, Assuman; Neema, Stella
Background Nodding syndrome has increasingly become an issue of public health concern internationally. The etiology of the disorder is still unknown and there are yet no curative treatments. We explored perceptions about treatment practices and barriers to health seeking for nodding syndrome in Pader and Kitgum districts in northern Uganda in order to provide data necessary for informing policy on treatment adherence and rehabilitations. Methods We used focus group discussions and individual interviews to gain deep insights into help-seeking and treatment practices for nodding syndrome. Purposive sampling was used to identify information-rich participants that included village health teams, community members not directly affected with nodding syndrome, district leaders, healthcare professionals, and caregivers of children affected with nodding syndrome. We used qualitative content analysis to analyze data and presented findings under distinct categories and themes. Results Caregivers and communities sought care from multiple sources including biomedical facilities, traditional healers, traditional rituals from shrines, and spiritual healing. Nodding syndrome affected children reportedly have showed no enduring improvement with traditional medicines, traditional rituals, and prayers. A substantial minority of participants reported minimal improvements in symptoms of convulsions with use of western medicines. Challenges involved in health seeking included; (1) health system factors e.g. long distances to facilities, frequent unavailability of medicines, few healthcare providers, and long waiting times; (2) contextual and societal challenges e.g. lack of money for transport and medical bills, overburdening nature of the illness that does not allow time for other activities, and practical difficulties involved in transporting the physically deformed and mentally retarded children to the health facilities. Conclusions Help-seeking for nodding syndrome is pluralistic and include use of traditional and biomedical practices. Western medicines admittedly showed at least short term control on nodding syndrome symptoms, especially convulsions and led in a few cases to regain of functional abilities. However, multiple barriers hinder health seeking and interfere with adherence to biomedical treatments. Regarding cure, there are hitherto no treatments participants perceive cure nodding syndrome.
Nodding Syndrome: Recent Insights into Etiology, Pathophysiology, and Treatment
(Dove press Ltd, 2018-05-24) Mwaka, Amos Deogratius; Semakula, Roy Jerome; Abbo, Catherine; Idro, Richard
Nodding syndrome is an enigmatic neuropsychiatric and epileptiform disorder associated with psychomotor, mental, and physical growth retardation. The disorder affects otherwise previously normal children aged 3–18 years, with a slight preponderance for the male child. Nodding syndrome has been described in rural regions of some low-income countries in sub-Saharan Africa including northern Uganda, South Sudan, and a mountainous region of southern Tanzania. The cause of the disorder has hitherto eluded scientists. Neuroimaging studies show involvement of the nervous system with associated severe cortical atrophy in the affected children. The affected communities have generated a number of perceived causes including some conspiracy theories related to intentional poisoning of water sources and foods, and causes related to fumes and chemicals from ammunitions used during civil wars in the affected regions. From biomedical perspectives, the treatment of the affected children is geared towards symptoms control and rehabilitation. There is evidence that seizures and behavioral problems including wandering and episodes of aggressions are controllable with anticonvulsants, especially sodium valproate and antipsychotics. No treatments have proven effective in reversing the course of the disorder, and cure remains a distant goal. Community members have used indigenous medicines, cleansing rituals, and prayer interventions, but have not perceived any reasonable improvements. A randomized controlled clinical trial is ongoing in northern Uganda to test the efficacy and effectiveness of doxycycline in the treatment of nodding syndrome. The hypothesis underlying the doxycycline trial underscores the role of antigenic mimicry: that antibodies generated against an antigen of a microorganism that resides inside the black fly-transmitted parasite, Onchocerca volvulus becomes directed against nervous tissue in the brain. This paper reviews some of the recent advances in researches on the etiologies, pathophysiology, and treatment of nodding syndrome.
Qualitative Evaluation of the Outcomes of Care and Treatment for Children and Adolescents With Nodding Syndrome and Other Epilepsies in Uganda
(BioMed Central Ltd, 2019-04-30) Abbo, Catherine; Mwaka, Amos Deogratius; Opar, Toliva Bernard; Idro, Richard
Background: In 2012, the Ugandan Government declared an epidemic of Nodding Syndrome (NS) in the Northern districts of Gulu, Kitgum, Lamwo and Pader. Treatment guidelines were developed and NS treatment centres were established to provide symptomatic control and rehabilitation. However, a wide gap remained between the pre defined care standards and the quality of routine care provided to those affected. This study is to qualitatively assess adherence to accepted clinical care standards for NS; identify gaps in the care of affected children and offer Clinical Support Supervision (CSS) to Primary Health Care (PHC) staff at the treatment centres; and identify psychosocial challenges faced by affected children and their caregivers. Methods: This case study was carried out in the districts of Gulu, Kitgum, Lamwo and Pader in Uganda from September to December in 2015. Employing the 5-stage approach of Clinical Audit, data were collected through direct observations and interviews with PHC providers working in public and private-not-for-profit health facilities, as well as with caregivers and political leaders. The qualitative data was analysed using Seidel model of data processing. Results: Clinical Audit and CSS revealed poor adherence to treatment guidelines. Many affected children had suboptimal NS management resulting in poor seizure control and complications including severe burns. Root causes of these outcomes were frequent antiepileptic drugs stock outs, migration of health workers from their work stations and psychosocial issues. There was hardly any specialized multidisciplinary team (MDT) to provide for the complex rehabilitation needs of the patients and a task shifting model with inadequate support supervision was employed, leading to loss of skills learnt. Reported psychosocial and psychosexual issues associated with NS included early pregnancies, public display of sexual behaviours and child abuse. Conclusions: Despite involvement of relevant MDT members in the development of multidisciplinary NS guidelines, multidisciplinary care was not implemented in practice. There is urgent need to review the NS clinical guidelines. Quarterly CSS and consistent anticonvulsant medication are needed at health facilities in affected communities. Implementation of the existing policies and programs to deal with the psychosocial and psychosexual issues that affect children with NS and other chronic conditions is needed
Traditional and Complementary Medicine Use Among Adult Cancer Patients Undergoing Conventional Treatment in Sub-Saharan Africa: A Scoping Review on the Use, Safety and Risks
(Dove press Ltd, 2020-05-20) Mwaka, Amos Deogratius; Abbo, Catherine; Kinengyere, Annet Alison
Background: Use of traditional and complementary medicine (T&CM) is very common among patients in sub-Saharan Africa (SSA). However, there are limited data on concurrent use of T&CM with conventional cancer therapies. In this scoping review, we sought to describe the (i) prevalence of use, (ii) types of medicine, (iii) reasons for taking T&CM, (iv) current knowledge on safety and risks, (v) characteristics of adult cancer patients who use T&CM, and (vi) perceived treatment outcomes among cancer patients undergoing conven tional cancer treatment in SSA. Methods: We conducted a systematic literature search for articles published in the English language in three scientific databases (PubMed, Embase and Web of Science). We used a scoping review approach to map relevant literature on T&CM use among cancer patients undergoing conventional cancer treatments. We assessed 96 articles based on titles and abstracts, and 23 articles based on full text. Twelve articles fulfilled preset eligibility criteria. Results: More than half of the included articles were from only two countries in SSA: Nigeria and Uganda. Median prevalence of use of T&CM was 60.0% (range: 14.1–79.0%). Median percent disclosure of use of T&CM to attending healthcare professionals was low at 32% (range: 15.3– 85.7%). The most common reasons for non-disclosure were: the doctor did not ask, the doctor would rebuke them for using T&CM, and the doctors do not know much about T&CM and so there is no need to share the issue of use with them. T&CM used by cancer patients included herbs, healing prayers and massage. Reported reasons for use of T&CM in 8 of 12 articles included the wish to get rid of cancer symptoms, especially pain, cure cancer, improve physical and psychological well-being, treat toxicity of conventional cancer therapies and improve immunity. There were limited data on safety and risk profiles of T&CM among cancer patients in SSA. Conclusion: Use of traditional and complementary medicines is common among cancer patients undergoing conventional cancer treatments. Healthcare professionals caring for cancer patients ought to inquire and communicate effectively regarding the use of T&CM in order to minimize the risks of side effects from concurrent use of T&CM and biomedicines.

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