8 research outputs found
Using Community-Owned Resource Persons to Provide Early Diagnosis and Treatment and Estimate Malaria Burden at Community Level in North-Eastern Tanzania.
Although early diagnosis and prompt treatment is an important strategy for control of malaria, using fever to initiate presumptive treatment with expensive artemisinin combination therapy is a major challenge; particularly in areas with declining burden of malaria. This study was conducted using community-owned resource persons (CORPs) to provide early diagnosis and treatment of malaria, and collect data for estimation of malaria burden in four villages of Korogwe district, north-eastern Tanzania.In 2006, individuals with history of fever within 24 hours or fever (axillary temperature ≥37.5°C) at presentation were presumptively treated using sulphadoxine/pyrimethamine. Between 2007 and 2010, individuals aged five years and above, with positive rapid diagnostic tests (RDTs) were treated with artemether/lumefantrine (AL) while under-fives were treated irrespective of RDT results. Reduction in anti-malarial consumption was determined by comparing the number of cases that would have been presumptively treated and those that were actually treated based on RDTs results. Trends of malaria incidence and slide positivity rates were compared between lowlands and highlands. Of 15,729 cases attended, slide positivity rate was 20.4% and declined by >72.0% from 2008, reaching <10.0% from 2009 onwards; and the slide positivity rates were similar in lowlands and highlands from 2009 onwards. Cases with fever at presentation declined slightly, but remained at >40.0% in under-fives and >20.0% among individuals aged five years and above. With use of RDTs, cases treated with AL decreased from <58.0% in 2007 to <11.0% in 2010 and the numbers of adult courses saved were 3,284 and 1,591 in lowlands and highlands respectively. Malaria incidence declined consistently from 2008 onwards; and the highest incidence of malaria shifted from children aged <10 years to individuals aged 10-19 years from 2009. With basic training, supervision and RDTs, CORPs successfully provided early diagnosis and treatment and reduced consumption of anti-malarials. Progressively declining malaria incidence and slide positivity rates suggest that all fever cases should be tested with RDTs before treatment. Data collected by CORPs was used to plan phase 1b MSP3 malaria vaccine trial and will be used for monitoring and evaluation of different health interventions. The current situation indicates that there is a remarkable changing pattern of malaria and these areas might be moving from control to pre-elimination levels
Satisfactory safety and immunogenicity of MSP3 malaria vaccine candidate in Tanzanian children aged 12-24 months.
BACKGROUND: Development and deployment of an effective malaria vaccine would complement existing malaria control measures. A blood stage malaria vaccine candidate, Merozoite Surface Protein-3 (MSP3), produced as a long synthetic peptide, has been shown to be safe in non-immune and semi-immune adults. A phase Ib dose-escalating study was conducted to assess the vaccine's safety and immunogenicity in children aged 12 to 24 months in Korogwe, Tanzania (ClinicalTrials.gov number: NCT00469651). METHODS: This was a double-blind, randomized, controlled, dose escalation phase Ib trial, in which children were given one of two different doses of the MSP3 antigen (15 microg or 30 microg) or a control vaccine (Engerix B). Children were randomly allocated either to the MSP3 candidate malaria vaccine or the control vaccine administered at a schedule of 0, 1, and 2 months. Immunization with lower and higher doses was staggered for safety reasons starting with the lower dose. The primary endpoint was safety and reactogenicity within 28 days post-vaccination. Blood samples were obtained at different time points to measure immunological responses. Results are presented up to 84 days post-vaccination. RESULTS: A total of 45 children were enrolled, 15 in each of the two MSP3 dose groups and 15 in the Engerix B group. There were no important differences in reactogenicity between the two MSP3 groups and Engerix B. Grade 3 adverse events were infrequent; only five were detected throughout the study, all of which were transient and resolved without sequelae. No serious adverse event reported was considered to be related to MSP3 vaccine. Both MSP3 dose regimens elicited strong cytophilic IgG responses (subclasses IgG1 and IgG3), the isotypes involved in the monocyte-dependant mechanism of Plasmodium falciparum parasite-killing. The titers reached are similar to those from African adults having reached a state of premunition. Furthermore, vaccination induced seroconversion in all vaccinees. CONCLUSION: The MSP3 malaria vaccine candidate was safe, well tolerated and immunogenic in children aged 12-24 months living in a malaria endemic community. Given the vaccine's safety and its induction of cytophilic IgG responses, its efficacy against P. falciparum infection and disease needs to be evaluated in Phase 2 studies
Population pharmacokinetic and pharmacodynamic properties of intramuscular quinine in Tanzanian children with severe Falciparum malaria.
Although artesunate is clearly superior, parenteral quinine is still used widely for the treatment of severe malaria. A loading-dose regimen has been recommended for 30 years but is still often not used. A population pharmacokinetic study was conducted with 75 Tanzanian children aged 4 months to 8 years with severe malaria who received quinine intramuscularly; 69 patients received a loading dose of 20 mg quinine dihydrochloride (salt)/kg of body weight. Twenty-one patients had plasma quinine concentrations detectable at baseline. A zero-order absorption model with one-compartment disposition pharmacokinetics described the data adequately. Body weight was the only significant covariate and was implemented as an allometric function on clearance and volume parameters. Population pharmacokinetic parameter estimates (and percent relative standard errors [%RSE]) of elimination clearance, central volume of distribution, and duration of zero-order absorption were 0.977 liters/h (6.50%), 16.7 liters (6.39%), and 1.42 h (21.5%), respectively, for a typical patient weighing 11 kg. Quinine exposure was reduced at lower body weights after standard weight-based dosing; there was 18% less exposure over 24 h in patients weighing 5 kg than in those weighing 25 kg. Maximum plasma concentrations after the loading dose were unaffected by body weight. There was no evidence of dose-related drug toxicity with the loading dosing regimen. Intramuscular quinine is rapidly and reliably absorbed in children with severe falciparum malaria. Based on these pharmacokinetic data, a loading dose of 20 mg salt/kg is recommended, provided that no loading dose was administered within 24 h and no routine dose was administered within 12 h of admission. (This study has been registered with Current Controlled Trials under registration number ISRCTN 50258054.)
Epidemiology of Malaria in an Area Prepared for Clinical Trials in Korogwe, North-eastern Tanzania.
Site preparation is a pre-requesite in conducting malaria vaccines trials. This study was conducted in 12 villages to determine malariometric indices and associated risk factors, during long and short rainy seasons, in an area with varying malaria transmission intensities in Korogwe district, Tanzania. Four villages had passive case detection (PCD) of fever system using village health workers. Four malariometric cross-sectional surveys were conducted between November 2005 and May 2007 among individuals aged 0-19 years, living in lowland urban, lowland rural and highland strata. A total of 10,766 blood samples were collected for malaria parasite diagnosis and anaemia estimation. Blood smears were stained with Giemsa while haemoglobin level was measured by HaemoCue. Socio-economic data were collected between Jan-Apr 2006. Adjusting for the effect of age, the risk of Plasmodium falciparum parasitaemia was significantly lower in both lowland urban, (OR = 0.26; 95%CI: 0.23-0.29, p < 0.001) and highlands, (OR = 0.21; 95%CI: 0.17-0.25, p < 0.001) compared to lowland rural. Individuals aged 6-9 years in the lowland rural and 4-19 years in both lowland urban and highlands had the highest parasite prevalence, whilst children below five years in all strata had the highest parasite density. Prevalence of splenomegaly and gametocyte were also lower in both lowland urban and highlands than in lowland rural. Anaemia (Hb <11 g/dl) prevalence was lowest in the lowland urban. Availability of PCD and higher socio-economic status (SES) were associated with reduced malaria and anaemia prevalence. Higher SES and use of bed nets in the lowland urban could be the important factors for low malaria infections in this stratum. Results obtained here were used together with those from PCD and DSS in selecting a village for Phase 1b MSP3 vaccine trial, which was conducted in the study area in year 2008
Persistance with non-functional problem solving in chronic pain
Research has demonstrated the relationship between persistence with problem solving focussed on pain removal and increased levels of distress in the chronic pain population. It has been suggested that one factor which motivates individuals to persist with pain removal strategies, despite repeated failed attempts, is their worries about the future. This can be conceptualised as the feared-for self. The purpose of this research was to investigate the relationship between problem solving strategies and the feared-for self in individuals with chronic pain. An additional aim of this research was to develop a new measure of problem solving requiring respondents to generate novel solutions to problem vignettes.
58 participants with chronic pain were recruited from specialist pain clinics. Participants completed the feared-for selves interview, a questionnaire measure of problem solving (PaSol), the new problem solving measure (MEPSP) and measures of pain severity (VAS), psychological distress(HADS), pain acceptance (CPAQ) and pain-related disability (PDI).
Persistence with pain removal (assimilative problem solving) was significantly correlated with proximity to the feared-for self and enmeshment with the feared-for self. Multiple regression analyses found mixed results. Proximity to the feared-for self was a significant predictor of assimilative problem solving when the MEPSP was used as the outcome variable but this was not replicated with the PaSol data. Enmeshment with the feared-for self was a significant predictor of assimilative problem solving when the PaSol was the outcome variable but this was not replicated with the MEPSP data.
This study has provided initial support for the relationship between the feared-for self and assimilative problem solving in the chronic pain population. However, further research is necessary to verify these findings. Initial results for the MEPSP suggest that further development of this measure is worthwhile. The clinical implications of these results are discussed along with suggestions for future research
Reading-related skills in earlier- and later-schooled children
We investigate the effects of age-related factors and formal instruction on the development of reading-related skills in children aged four and seven years. Age effects were determined by comparing two groups of children at the onset of formal schooling; one aged seven (later-schooled) and one aged four (earlier-schooled). Schooling effects were measured by comparing the later-schooled group with earlier-schooled age-matched controls. There were significant effects of age and schooling on phonological awareness and visual-verbal learning, and an effect of age, but not schooling, on vocabulary and short-term verbal memory. We conclude that age-related factors and reading instruction contribute to the development of phoneme awareness and that vocabulary and verbal memory improve with age
Evidence of artemisinin partial resistance in northwestern Tanzania: clinical and molecular markers of resistance
Background In 2021, nationwide malaria molecular surveillance revealed a high prevalence of a validated artemisinin resistance marker, the kelch13 (k13) Arg561His mutation, in the Kagera region of northwestern Tanzania. We aimed to investigate the efficacy of artemether-lumefantrine and artesunate-amodiaquine and to confirm the presence of artemisinin partial resistance (ART-R) in the Karagwe district of this region. Methods This single-arm, therapeutic efficacy study was carried out at the Bukangara dispensary in the Karagwe district of the Kagera region in northwestern Tanzania. Eligible participants were aged between 6 months and 120 months, had confirmed Plasmodium falciparum asexual parasitaemia, and met other inclusion criteria according to WHO's standard protocol. Participants were enrolled, treated sequentially with either artemether-lumefantrine or artesunate-amodiaquine, and assessed clinically and parasitologically for 28 days as per WHO protocol. Parasitaemia was measured every 8 h until day 3, on day 7, and then during weekly follow-up visits until day 28. Mutations in the k13 gene and extended haplotypes with the mutations were analysed, and comparisons were made with previous samples collected in the same region of Kagera and in Rwanda and southeast Asia. The primary endpoint was PCRcorrected cure rate. Findings Between April 29 and Sept 1, 2022, 343 patients were screened, of whom 176 were enrolled: 88 in each treatment group. The PCR-corrected cure rate was 98% (95% CI 91-100) in the artemether-lumefantrine group and 100% (96-100) in the artesunate-amodiaquine group. Persistent parasitaemia on day 3 occurred in 11 (13%) of 88 patients in the artemether-lumefantrine group and 17 (19%) of 88 patients in the artesunate-amodiaquine group. Arg561His mutations on day 0 and parasitaemia on day 3 were reported in eight (9%) of 87 patients in the artemether- lumefantrine group and ten (12%) of 86 patients in the artesunate-amodiaquine group. The median parasite clearance half-life in patients harbouring parasites with Arg561His mutation was 61 h in the artemether-lumefantrine group and 60 h in the artesunate-amodiaquine group. Parasites with the Arg561His mutation were not similar to those from southeast Asia and Rwanda but had similar haplotypes to parasites reported in the same Tanzanian region of Kagera in 2021. Interpretation This study confirms the presence of ART-R in Tanzania, although artemether-lumefantrine and artesunate-amodiaquine showed high efficacy. A context-specific response strategy and vigilance to detect the reduced efficacy of current antimalarial treatments and ART-R in other parts of the country are urgently needed. Funding The Bill & Melinda Gates Foundation and the US National Institutes of Health. Copyright (c) 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
The Effects of a Shared Reading Intervention on the English Reading Skills of Year One Students in a Level Two Māori-medium Educational Context
One of the biggest challenges confronting literacy education in Aotearoa New Zealand is accommodating the differences in English reading-related variables at school entry to produce equitable outcomes in later reading achievement (Wilkinson, Freebody, & Elkins, 2000). English-medium schools in Aotearoa struggle to negotiate effective literacy practices that validate and cater for the cognitive, cultural, and linguistic differences children bring to the process of learning to read in English. Whereas, the role of English reading instruction in Māori-medium schools has been an under-researched and controversial issue. How to accommodate for these differences to achieve equitable English reading outcomes in a year 1 level 2 Māori-medium context is the theme that this research seeks to explore.
This Masters thesis reports on a shared reading intervention that explicitly teaches phonological awareness and alphabet knowledge to examine its effects on the English reading skills of year 1 students in a level 2 Māori-medium setting. The research implemented a Kaupapa Māori framework and used interviews, surveys, reliable literacy measures, and research-based literacy instruction to explore reading acquisition for this particular cohort. Thus, the purposes of the study were (a) to glean an in-depth understanding of the literacy and language practices that potentially shaped the participants English reading–related variables, (b) to examine the range of English reading-related skills for this cohort, and (c) to determine the effects of the intervention on their English reading skills.
Eight students were divided and matched with a pair according to their reported pre-test phonemic awareness and alphabet knowledge scores, and then randomly assigned to either an intervention (n = 4) or treatment control (n = 4) group. The intervention programme was carried out over a six week period and comprised 12, 30 minute lessons that integrated phonological and alphabetic based decoding skills within the shared reading approach. The duration of the treatment control programme was also carried out over a six week period and comprised 12, 30 minutes lessons that integrated semantic, syntactic, and visual graphophonic sources of information to recognise words. The results indicated the breadth and depth of English reading skills in year 1 level 2 Māori-medium contexts are diverse and the children had a positive attitude and sense of efficacy towards reading. A comparison of the test results between the intervention and treatment control group demonstrated that a shared reading intervention that focused explicitly on phonological awareness and alphabet knowledge is effective in raising letter-naming knowledge, pseudoword decoding, phonemic awareness, and invented spelling. The results are discussed in light of theoretical assumptions about reading acquisition that underlie word-base and text-base approaches to word recognition.
Overall, this study supports the development and reform of training and professional development opportunities in phonological awareness and alphabet knowledge to better support, inform, and educate Aotearoa reading teachers. This study contributes to the knowledge of English reading acquisition that validate the depth and breadth of early cognitive and linguistic differences to increase equitable English reading outcomes in level 2 Māori-medium contexts
