Relationship Between Alpha+-Thalassaemia and Glutathione-S-Transferases Polymorphisms in Children with Severe Malaria in Tanzania

Alpha+-thalassaemia is well known for conferring partial protection to against severe malaria. On the other, Glutathione –S-transferase (GST) polymorphism has recently been associated to severe malaria in children. A retrospective cross sectional study was carried out to determine the relationship between genotypic polymorphisms of alpha+-thalassaemia and glutathione-S-transferase in children with severe malaria. A total of 148 DNA samples from children aged between 1 and 15 years with mild and severe malaria were retrieved and determined by polymerase chain reaction. Children with Glutathione-S-transferase-pi1 (GSTP1)-polymorphism were observed to have three fold risk (OR = 2.9; 95% CI =1.3- 6.1; P = 0.006) of developing severe malaria compared to mild malaria in Mnyuzi-Korogwe, north-eastern, Tanzania. In the presence of Glutathione- S-transferase-pi1 polymorphism, children were found to have 3% decreased protective effect of alpha+- thalassaemia polymorphisms (homozygotes and heterozygotes) against severe malaria although this was not statistically significant [ OR = 0.81 (95% CI = 0.5-1.5; P = 0.5) to OR = 0.78 (95% CI = 0.4-1.5; P = 0.44)]. We conclude that Glutathione-S-transferase-pi1 polymorphism increases risk of developing severe malaria due to Plasmodium falciparum in children. The observed inverse relationship between GSTP1 polymorphisms and alpha+-thalassaemia to children with severe malaria need further investigation

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

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

Migration of a Research Library's ICT-Based Services to a Cloud Platform

Libraries have been at the forefront in adopting emerging technologies to manage the library’s operations and provide information services to the user community they serve. With the emergence of cloud computing (CC) technology, libraries are exploring and adopting CC service models to make their own services more efficient, reliable, secure, scalable, and cost-effective. In this article, the authors share their experience migrating some of the library’s locally hosted ICT-based services onto the Microsoft Azure cloud platform. The migration of services to a cloud platform has helped the library significantly reduce the downtime of its services due to power or network or system outages

Acceptability of malaria rapid diagnostic tests administered by village health workers in Pangani District, North eastern Tanzania.

BACKGROUND: Malaria continues to top the list of the ten most threatening diseases to child survival in Tanzania. The country has a functional policy for appropriate case management of malaria with rapid diagnostic tests (RDTs) from hospital level all the way to dispensaries, which are the first points of healthcare services in the national referral system. However, access to these health services in Tanzania is limited, especially in rural areas. Formalization of trained village health workers (VHWs) can strengthen and extend the scope of public health services, including diagnosis and management of uncomplicated malaria in resource-constrained settings. Despite long experience with VHWs in various health interventions, Tanzania has not yet formalized its involvement in malaria case management. This study presents evidence on acceptability of RDTs used by VHWs in rural northeastern Tanzania. METHODS: A cross-sectional study using quantitative and qualitative approaches was conducted between March and May 2012 in Pangani district, northeastern Tanzania, on community perceptions, practices and acceptance of RDTs used by VHWs. RESULTS: Among 346 caregivers of children under 5 years old, no evidence was found of differences in awareness of HIV rapid diagnostic tests and RDTs (54 vs. 46 %, p = 0.134). Of all respondents, 92 % expressed trust in RDT results, 96 % reported readiness to accept RDTs by VHWs, while 92 % expressed willingness to contribute towards the cost of RDTs used by VHWs. Qualitative results matched positive perceptions, attitudes and acceptance of mothers towards the use of RDTs by VHWs reported in the household surveys. Appropriate training, reliable supplies, affordability and close supervision emerged as important recommendations for implementation of RDTs by VHWs. CONCLUSION: RDTs implemented by VHWs are acceptable to rural communities in northeastern Tanzania. While families are willing to contribute towards costs of sustaining these services, policy decisions for scaling-up will need to consider the available and innovative lessons for successful universally accessible and acceptable services in keeping with national health policy and sustainable development goals

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

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.

Despite 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

Lost to follow up and clinical outcomes of HIV adult patients on antiretroviral therapy in care and treatment centres in Tanga City, north-eastern Tanzania

Scaling up of Antiretroviral (ARV) drugs is crucial and should be a perpetual venture in developing countries in-order to increase the survival period of HIV/AIDS individuals. In Tanzania, information on the rate of patients considered as lost to follow up during treatment with ARVs is scarce. The objective of this study was to determine the rate of lost to follow up and treatment outcome among patients attending two care and treatment clinics (CTCs) in Tanga City in north-eastern Tanzania. A descriptive observational study was carried out on cohorts from Tanga AIDS Working Group and Bombo Regional Hospital. The total number of patients identified as “lost to follow up” were 89 of which 14 (15.7%) died. Among those who died, 3 (21.4%) died between the second week and 3 months after ARV initiation. Of those still alive (84.3%; 75/89), 25% (19/75) were still on ARVs, whereas 47 (62.7%) self transferred to other CTCs. Proper patient documentation with actual residence address is a crucial aspect for adherence. Similarly, frequent prompt tracing of patient should be part of any drug interventional programme linking   facility and communities