333 research outputs found
Accuracy of Malaria Rapid Diagnostic Tests in Community Studies and their Impact on Treatment of Malaria in an Area with Declining Malaria Burden in North-Eastern Tanzania.
No full textDespite some problems related to accuracy and applicability of malaria rapid diagnostic tests (RDTs), they are currently the best option in areas with limited laboratory services for improving case management through parasitological diagnosis and reducing over-treatment. This study was conducted in areas with declining malaria burden to assess; 1) the accuracy of RDTs when used at different community settings, 2) the impact of using RDTs on anti-malarial dispensing by community-owned resource persons (CORPs) and 3) adherence of CORPs to treatment guidelines by providing treatment based on RDT results. Data were obtained from: 1) a longitudinal study of passive case detection of fevers using CORPs in six villages in Korogwe; and 2) cross-sectional surveys (CSS) in six villages of Korogwe and Muheza districts, north-eastern, Tanzania. Performance of RDTs was compared with microscopy as a gold standard, and factors affecting their accuracy were explored using a multivariate logistic regression model. Overall sensitivity and specificity of RDTs in the longitudinal study (of 23,793 febrile cases; 18,154 with microscopy and RDTs results) were 88.6% and 88.2%, respectively. In the CSS, the sensitivity was significantly lower (63.4%; χ2=367.7, p<0.001), while the specificity was significantly higher (94.3%; χ2=143.1, p<0.001) when compared to the longitudinal study. As determinants of sensitivity of RDTs in both studies, parasite density of<200 asexual parasites/μl was significantly associated with high risk of false negative RDTs (OR≥16.60, p<0.001), while the risk of false negative test was significantly lower among cases with fever (axillary temperature ≥37.5 °C) (OR≤0.63, p≤0.027). The risk of false positive RDT (as a determinant of specificity) was significantly higher in cases with fever compared to afebrile cases (OR≥2.40, p<0.001). Using RDTs reduced anti-malarials dispensing from 98.9% to 32.1% in cases aged ≥5 years. Although RDTs had low sensitivity and specificity, which varied widely depending on fever and parasite density, using RDTs reduced over-treatment with anti-malarials significantly. Thus, with declining malaria prevalence, RDTs will potentially identify majority of febrile cases with parasites and lead to improved management of malaria and non-malaria fevers
Clinical epidemiology of malaria related morbidities among school-aged children in Tanzania: A focus on Impact of Intermittent preventive treatment of malaria in school children
No full textAbstract: Compared to the general population, school-aged children harbour high malaria parasitaemia in most endemic areas of sub-Saharan Africa. In most cases, these children remain asymptomatic, which makes them vulnerable for anaemia and impaired cognitive ability. Data from malaria preventive therapies support the hypothesis that clearing, otherwise untreated, asymptomatic infections may provide a window of opportunity for haematological recovery by decreasing the rate of destruction and removal of parasitized red blood cells and improving the erythrocyte production rate in the bone marrow. Several studies have shown intermittent preventive treatment of malaria in schoolchildren (IPTsc) to be a feasible and effective tool to reduce malaria and malaria related anaemia. Despite this, well-known concepts to help school aged children, none has generated solution ready to use in a pragmatic way leading to policy and practice of the suggested intervention (IPTsc). This thesis show evidence on the burden of asymptomatic malaria in school children (chapter 3,4 and 5), then evidence on impact of IPTsc intervention on schoolchildren (chapter 6) and how could such an intervention be scaled up pragmatically and into policy (chapter 7,8 and 9). Research findings are based from two studies conducted in Muheza (clinical trial covering 7 primary schools recruiting 1566 schoolchildren- NCT03640403) and Handeni (TC and DC) and Kilindi DC\ua0 (implementation research covering over 127 primary schools with over 73000 schoolchildren- NCT04245033). This thesis has generated enough evidence that IPTsc is an important intervention reducing the malaria burden and its consequences in school age children with additional benefit on shrinking the reservoir in high endemic communities. The thesis comes up with a policy brief (chapter 9) developed to guide the introduction and practice of IPTsc in moderate to high endemic areas as recommended by the WHO malaria guideline 2023
Factors for unequal distribution of primary school teachers in Ruangwa District council, Tanzania
No full textThis study attempts to explore the factors for continuing existence of unequal distribution of teachers in Ruangwa District council, Tanzania. To capture the objectives of this study random and purposive sampling techniques were employed in the selection of a sample of 160 respondents out of a total of a population of 479. The findings suggest that a combination of lack of motivation and incentives; attrition; poor recruitment and deployment policy; preference to work in certain areas; lack of opportunity to career development; access to social service such as health care; and teachers’ mobility are the factors responsible for inequitable distribution of teachers in Ruangwa District council. Therefore this study recommends the government devises a good strategy for motivating teachers to accept posts in remote rural areas. Comprehensive deployments policies need to be developed that ensure sufficient teachers in remote schools. Key Words: Education; Tanzania; Attrition; Teachers, Equitable Distribution
Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data.
No full textBACKGROUND: The efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial. Early results show significant, albeit partial, protection against clinical malaria and severe malaria. To ascertain variations in vaccine efficacy according to covariates such as transmission intensity, choice of adjuvant, age at vaccination, and bednet use, we did an individual-participant pooled analysis of phase 2 clinical data. METHODS: We analysed data from 11 different sites in Africa, including 4453 participants. We measured heterogeneity in vaccine efficacy by estimating the interactions between covariates and vaccination in pooled multivariable Cox regression and Poisson regression analyses. Endpoints for measurement of vaccine efficacy were infection, clinical malaria, severe malaria, and death. We defined transmission intensity levels according to the estimated local parasite prevalence in children aged 2-10 years (PrP₂₋₁₀), ranging from 5% to 80%. Choice of adjuvant was either AS01 or AS02. FINDINGS: Vaccine efficacy against all episodes of clinical malaria varied by transmission intensity (p=0·001). At low transmission (PrP₂₋₁₀ 10%) vaccine efficacy was 60% (95% CI 54 to 67), at moderate transmission (PrP₂₋₁₀ 20%) it was 41% (21 to 57), and at high transmission (PrP₂₋₁₀ 70%) the efficacy was 4% (-10 to 22). Vaccine efficacy also varied by adjuvant choice (p<0·0001)--eg, at low transmission (PrP₂₋₁₀ 10%), efficacy varied from 60% (95% CI 54 to 67) for AS01 to 47% (14 to 75) for AS02. Variations in efficacy by age at vaccination were of borderline significance (p=0·038), and bednet use and sex were not significant covariates. Vaccine efficacy (pooled across adjuvant choice and transmission intensity) varied significantly (p<0·0001) according to time since vaccination, from 36% efficacy (95% CI 24 to 45) at time of vaccination to 0% (-38 to 38) after 3 years. INTERPRETATION: Vaccine efficacy against clinical disease was of limited duration and was not detectable 3 years after vaccination. Furthermore, efficacy fell with increasing transmission intensity. Outcomes after vaccination cannot be gauged accurately on the basis of one pooled efficacy figure. However, predictions of public-health outcomes of vaccination will need to take account of variations in efficacy by transmission intensity and by time since vaccination. FUNDING: Medical Research Council (UK); Bill & Melinda Gates Foundation Vaccine Modelling Initiative; Wellcome Trust
Decreasing incidence of severe malaria and community-acquired bacteraemia among hospitalized children in Muheza, north-eastern Tanzania, 2006-2010.
No full textBACKGROUND: The annual incidence and temporal trend of severe malaria and community-acquired bacteraemia during a four-year period in Muheza, Tanzania was assessed. METHODS: Data on severely ill febrile children aged 2 months to 14 years from three prospective studies conducted at Muheza District Hospital from 2006 to 2010 was pooled and analysed. On admission, each enrolled child had a thin and thick blood film and at least one rapid diagnostic test for falciparum malaria, as well as a blood culture. The annual incidence of bacteraemia and severe malaria among children coming from Muheza was calculated and their temporal trend was assessed. RESULTS: Overall, 1, 898 severe falciparum malaria and 684 bacteraemia cases were included. Of these, 1, 356 (71%) and 482 (71%), respectively, were from the referral population of Muheza. The incidence of falciparum malaria and all-cause bacteraemia in Muheza decreased five-fold and three-fold, respectively, from the first to the fourth year of surveillance (p < 0.0001). During this period, the median ages of children from Muheza admitted with severe malaria increased from 1.7 to 2.5 years (p < 0.0001). The reduction in all-cause bacteraemia was mainly driven by the 11-fold decline in the incidence of non-typhoidal salmonellosis. The annual incidences of Haemophilus influenzae and pneumococcal invasive bacterial infections decreased as well but were much fewer in number. CONCLUSIONS: These results add to the growing evidence of the decline in malaria associated with a decrease in non-typhoidal salmonellosis and possibly other bacteraemias. Malarial prevention and control strategies may provide a greater benefit than the mere reduction of malaria alone
Altitude-dependent and -independent variations in Plasmodium falciparum prevalence in northeastern Tanzania.
No full textBACKGROUND: Effective malaria control requires information about intensity of transmission across large areas and populations. Estimates based on entomological factors lack precision and are not cost-effective to obtain. We tested altitude and rainfall measurements as correlates of transmission intensity in different ecological settings. METHODS: We conducted 2 cross-sectional surveys of approximately 12,000 people (1-45 years old) in 6 altitude transects (150-1800 m) in the Kilimanjaro and Tanga regions of Tanzania. Data were analyzed for associations with altitude and rainfall estimates by use of appropriate regression models. RESULTS: Plasmodium falciparum prevalence showed a negative relationship with altitude (19% and 21% decrease/100-m altitude increase, respectively, in children in Kilimanjaro and Tanga) and rainfall during the 3 months before the survey (46% decrease/100-mm rainfall increase in children in Kilimanjaro). Mean hemoglobin concentrations increased with altitude (0.05 and 0.09 g/dL/100-m altitude increase, respectively, in children in Kilimanjaro and Tanga) and rainfall (0.17 g/dL/100-mm rainfall increase in children and adults in Kilimanjaro). DISCUSSION: Altitude and rainfall were correlated with parasite prevalence and mean hemoglobin concentration; however, the relationship varied according to ecological setting. Climatological variables alone cannot predict malarial outcomes. Local variations in seasonality of malaria transmission--together with vector species composition, topography, host and parasite genetics, and socioeconomic factors--may influence malaria prevalence
Infection during Pregnancy
No full textSequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM) is scarce. We conducted a longitudinal, prospective study, both in Benin and Tanzania, including ∼1000 pregnant women in each site with systematic follow-up at scheduled antenatal visits until delivery. We used ex vivo flow cytometry to identify peripheral blood mononuclear cell (PBMC) profiles that are associated with PAM and anaemia, determining the phenotypic composition and activation status of PBMC in selected sub-groups with and without PAM both at inclusion and at delivery in a total of 302 women. Both at inclusion and at delivery PAM was associated with significantly increased frequencies both of B cells overall and of activated B cells. Infection-related profiles were otherwise quite distinct at the two different time-points. At inclusion, PAM was associated with anaemia, with an increased frequency of immature monocytes and with a decreased frequency of regulatory T cells (Treg). At delivery, infected women presented with significantly fewer plasmacytoid dendritic cells (DC), more myeloid DC expressing low levels of HLA-DR, and more effector T cells (Teff) compared to uninfected women. Independent associations with an increased risk of anaemia were found for altered antigen-presenting cell frequencies at inclusion, but for an increased frequency of Teff at delivery. Our findings emphasize the prominent role played by B cells during PAM whenever it arises during pregnancy, whilst also revealing signature changes in other circulating cell types that, we conclude, primarily reflect the relative duration of the infections. Thus, the acute, recently-acquired infections present at delivery were marked by changes in DC and Teff frequencies, contrasting with infections at inclusion, considered chronic in nature, that were characterized by an abundance of immature monocytes and a paucity of Treg in PBMC
Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination:A Phase 3 Randomized, Controlled Trial in Children and Young Infants at 11 African Sites
No full textBACKGROUND: A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission.METHODS AND FINDINGS: 6,537 infants aged 6-12 wk and 8,923 children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p<0.01 across all sites). VE during the 20 mo after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT). VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 33%], ITT), with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization. Post-vaccination anti-circumsporozoite antibody geometric mean titer varied from 348 to 787 EU/ml across sites in children and from 117 to 335 EU/ml in infants (per protocol). VE waned over time in both age categories (Schoenfeld residuals p<0.001). The number of clinical and severe malaria cases averted per 1,000 children vaccinated ranged across sites from 37 to 2,365 and from -1 to 49, respectively; corresponding ranges among infants were -10 to 1,402 and -13 to 37, respectively (ITT). Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively.CONCLUSIONS: RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. VE was higher in children than in infants, but even at modest levels of VE, the number of malaria cases averted was substantial. RTS,S/AS01 could be an important addition to current malaria control in Africa.TRIAL REGISTRATION: www.ClinicalTrials.gov NCT00866619 Please see later in the article for the Editors' Summary.</p
Challenges in malaria control in Sub-Saharan Africa: the vaccine perspective
No full textMalaria is a life-threatening disease of public health importance,
especially in sub-Saharan Africa. It is estimated that about 500
million cases of malaria occur annually and among these 1 million die
annually. Children below five years and pregnant women are the most
vulnerable groups. Several malaria control measures have been applied
such as environmental improvements, use of insecticide impregnated
nets, residual indoor spraying, early case detection and treatment with
effective antimalarial drugs. However, the adaptation of vector and
parasite has so far limited the effect of these interventions. The
emergence of resistance against drugs and insecticides requires in
response a steady stream of new interventions. Up to the beginning of
this millennium, most sub-Saharan African countries have been using
chloroquine (CQ) as the first-line antimalarial drug, which had to be
replaced with sulphadoxine-pyrimethamine (SP) after resistant parasites
had rendered CQ ineffective. Currently the first line treatment of
malaria consists of combination therapy which includes an artemisinin
derivative. The current approach appears robust but history has taught
us to be alert and to expect resistance to emerge. There is a pressing
need to develop and deploy complimentary strategies. Adding a
protective vaccine to the existing control tools for malaria holds
great promise yet no malaria vaccine has ever been licensed despite a
large number of attempts. The complexity of malaria parasites and the
ability of the parasite to suppress and evade immune responses are
formidable challenges. Fortunately, there are several promising
antimalarial vaccine candidates in the development pipeline. The most
promising vaccine candidate is RTSS which is currently tested in
various countries in sub-Saharan Africa, including two sites in
Tanzania. There is a hope that malaria vaccines could be developed and
deployed in malaria endemic communities. This article highlights the
challenges of developing and deploying malaria vaccines
Challenges in malaria control in sub-Saharan Africa: the vaccine perspective
No full textUdgivelsesdato: 2008-OctMalaria is a life-threatening disease of public health importance, especially in sub-Saharan Africa. It is estimated that about 500 million cases of malaria occur annually and among these 1 million die annually. Children below five years and pregnant women are the most vulnerable groups. Several malaria control measures have been applied such as environmental improvements, use of insecticide impregnated nets, residual indoor spraying, early case detection and treatment with effective antimalarial drugs. However, the adaptation of vector and parasite has so far limited the effect of these interventions. The emergence of resistance against drugs and insecticides requires in response a steady stream of new interventions. Up to the beginning of this millennium, most sub-Saharan African countries have been using chloroquine (CQ) as the first-line antimalarial drug, which had to be replaced with sulphadoxine-pyrimethamine (SP) after resistant parasites had rendered CQ ineffective. Currently the first line treatment of malaria consists of combination therapy which includes an artemisinin derivative. The current approach appears robust but history has taught us to be alert and to expect resistance to emerge. There is a pressing need to develop and deploy complimentary strategies. Adding a protective vaccine to the existing control tools for malaria holds great promise yet no malaria vaccine has ever been licensed despite a large number of attempts. The complexity of malaria parasites and the ability of the parasite to suppress and evade immune responses are formidable challenges. Fortunately, there are several promising antimalarial vaccine candidates in the development pipeline. The most promising vaccine candidate is RTSS which is currently tested in various countries in sub-Saharan Africa, including two sites in Tanzania. There is a hope that malaria vaccines could be developed and deployed in malaria endemic communities. This article highlights the challenges of developing and deploying malaria vaccines
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