Association between serum transferrin receptor levels and malaria recurrence in a malaria endemic area in Tanzania

Background: The relationship between body iron levels and malaria presents a complex interaction that provide variable and contradicting results. We designed a study to investigate associations between concentrations of biomarkers of body iron and malaria recurrence among children.Methods: We conducted a longitudinal descriptive community based study in a malaria endemic area in north- eastern Tanzania. The study involved 428 children of ≤5 years of age who were positive for malaria. Over a period of 6 months, sick children visited the study clinic for screening of malaria and measurement of iron storage biomarkers by serological assays. Correlations between levels of biomarkers and malaria was determined by Spearman correlations and Mann-Whitney U-Test. Associations between malaria recurrence and serum levels of iron biomarkers were determined by odds ratio (OR) with significance cut-off points of <0.15 in univariate and <0.05 in multivariate logistic regression analyses.Results: Only serum Transferrin Receptor (sTfR) levels had a positive correlation with malaria recurrence. When Mann-Whitney U test was used higher Hepcidin, sTfR and Leptin levels were significantly associated with malaria recurrence when malaria incidence was grouped into ‘once’ versus ‘more than once’. When malaria incidence was recategorised to ‘up to twice’ versus ‘more than twice’, only higher level of sTfR was associated with recurrence of malaria. With univariate regression analysis, only sTfR was found to be significantly associated with malaria recurrence, although this associated was not observed in Multivariate analyses.Conclusion: Despite the absence of association in multivariate analyses, univariate analyses suggest elevated levels of sTFR as a likely predictor of Plasmodium falciparum re-infection.      

Overuse of artemisinin-combination therapy in Mto wa Mbu (river of mosquitoes), an area misinterpreted as high endemic for malaria

BACKGROUND: Adequate malaria diagnosis and treatment remain major difficulties in rural sub-Saharan Africa. These issues deserve renewed attention in the light of first-line treatment with expensive artemisinin-combination therapy (ACT) and changing patterns of transmission intensity. This study describes diagnostic and treatment practices in Mto wa Mbu, an area that used to be hyperendemic for malaria, but where no recent assessments of transmission intensity have been conducted. METHODS: Retrospective and prospective data were collected from the two major village health clinics. The diagnosis in prospectively collected data was confirmed by microscopy. The level of transmission intensity was determined by entomological assessment and by estimating sero-conversion rates using anti-malarial antibody responses. RESULTS: Malaria transmission intensity by serological assessment was equivalent to 40% of outpatients attending the clinics in 2006-2007 were diagnosed with malaria. Prospective data demonstrated a very high overdiagnosis of malaria. Microscopy was unreliable with < 1% of slides regarded as malaria parasite-positive by clinic microscopists being confirmed by trained research microscopists. In addition, many 'slide negatives' received anti-malarial treatment. As a result, 99.6% (248/249) of the individuals who were treated with ACT were in fact free of malaria parasites. CONCLUSION: Transmission intensity has dropped considerably in the area of Mto wa Mbu. Despite this, most fevers are still regarded and treated as malaria, thereby ignoring true causes of febrile illness and over-prescribing ACT. The discrepancy between the perceived and actual level of transmission intensity may be present in many areas in sub-Saharan Africa and calls for greater efforts in defining levels of transmission on a local scale to help rational drug-prescribing behaviour

Defining malaria burden from morbidity and mortality records, self treatment practices and serological data in Magugu, Babati District, northern Tanzania

Malaria morbidity and mortality data from clinical records provide essential information towards defining disease burden in the area and for planning control strategies, but should be augmented with data on transmission intensity and serological data as measures for exposure to malaria. The objective of this study was to estimate the malaria burden based on serological data and prevalence of malaria, and compare it with existing self-treatment practices in Magugu in Babati District of northern Tanzania. Prospectively, 470 individuals were selected for the study. Both microscopy and Rapid Diagnostic Test (RDT) were used for malaria diagnosis. Seroprevalence of antibodies to merozoite surface proteins (MSP-119) and apical membrane antigen (AMA-1) was performed and the entomological inoculation rate (EIR) was estimated. To complement this information, retrospective data on treatment history, prescriptions by physicians and use of bed nets were collected. Malaria prevalence in the area was 6.8% (32/470). Of 130 individuals treated with artemisinin combination therapy (ACT), 22.3 % (29/130) were slide confirmed while 75.3% (98/130) of them were blood smear negative. Three of the slides confirmed individuals were not treated with ACT. Fever was reported in 38.2% of individuals, of whom 48.8 % (88/180) were given ACT. Forty-two (32.3%) of those who received ACT had no history of fever. About half (51.1%) of those treated with ACT were childre

Prevalence of asymptomatic malaria infections in selected military camps in Tanzania

Background: Despite a decrease in malaria burden reported between 2000 and 2015, an increasing trend of malaria transmission has been recently reported in some endemic countries including Tanzania. Periodic monitoring to identify pocket areas for asymptomatic Plasmodium falciparum infection&nbsp; &nbsp;is vital for malaria elimination efforts. The objective of this study was to determine prevalence of asymptomatic malaria infections among military recruits in selected camps in Tanzania. Methods: A cross-sectional study was conducted in 2015 at four military camps (Bulombora, Mgambo, Ruvu, and Rwamkoma) of National Service located in regions with varying malaria endemicity in Tanzania.&nbsp; Finger prick blood samples collected from asymptomatic military recruits who had been at the camps for over two months were simultaneously tested using microscopy and malaria rapid diagnostic tests (mRDTs) to detect malaria parasite infections. Results: Malaria parasite prevalence among asymptomatic recruits was 20.3% and 19.4% by microscopy and mRDT respectively. There was moderate agreement (Kappa=0.724) between microscopy and mRDT test results. A significant difference (p&lt;0.001) of malaria parasite prevalence among the four study camps was observed; ranging from 1.9% in Bulombora to 39.4% in Rwamkoma. The geometric mean parasite density was 11,053 asexual parasites/µl and most recruits (56.8%) had 200 to 1999 asexual parasites/µl. P. falciparum was the predominant (99.2%) malaria parasite species. Conclusion: Our study found high prevalence of asymptomatic malaria infections among military recruits in the selected camps, and this varied from one camp to another. The study has highlighted that public residence institutions such as military camps can be potential hotspots for malaria infection and therefore should not be skipped in routine national malaria surveillance system for monitoring trends of infection

A cluster-randomized trial of mass drug administration with a gametocytocidal drug combination to interrupt malaria transmission in a low endemic area in Tanzania

Contains fulltext : 96570.pdf (publisher's version ) (Open Access)BACKGROUND: Effective mass drug administration (MDA) with anti-malarial drugs can clear the human infectious reservoir for malaria and thereby interrupt malaria transmission. The likelihood of success of MDA depends on the intensity and seasonality of malaria transmission, the efficacy of the intervention in rapidly clearing all malaria parasite stages and the degree to which symptomatic and asymptomatic parasite carriers participate in the intervention. The impact of MDA with the gametocytocidal drug combination sulphadoxine-pyrimethamine (SP) plus artesunate (AS) plus primaquine (PQ, single dose 0.75 mg/kg) on malaria transmission was determined in an area of very low and seasonal malaria transmission in northern Tanzania. METHODS: In a cluster-randomized trial in four villages in Lower Moshi, Tanzania, eight clusters (1,110 individuals; cluster size 47- 209) were randomized to observed treatment with SP+AS+PQ and eight clusters (2,347 individuals, cluster size 55- 737) to treatment with placebo over three days. Intervention and control clusters were 1 km apart; households that were located between clusters were treated as buffer zones where all individuals received SP+AS+PQ but were not selected for the evaluation. Passive case detection was done for the entire cohort and active case detection in 149 children aged 1-10 year from the intervention arm and 143 from the control arm. Four cross-sectional surveys assessed parasite carriage by microscopy and molecular methods during a five-month follow-up period. RESULTS: The coverage rate in the intervention arm was 93.0% (1,117/1,201). Parasite prevalence by molecular detection methods was 2.2-2.7% prior to the intervention and undetectable during follow-up in both the control and intervention clusters. None of the slides collected during cross-sectional surveys had microscopically detectable parasite densities. Three clinical malaria episodes occurred in the intervention (n = 1) and control clusters (n = 2). CONCLUSIONS: This study illustrates the possibility to achieve high coverage with a three-day intervention but also the difficulty in defining suitable outcome measures to evaluate interventions in areas of very low malaria transmission intensity. The decline in transmission intensity prior to the intervention made it impossible to assess the impact of MDA in the chosen study setting. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00509015

Transmission intensity and malaria vector population structure in Magugu, Babati District in northern Tanzania

A 1-year longitudinal study was conducted in Magugu in Babati district, northern Tanzania to determine malaria vector population structure and malaria transmission indices. Mosquitoes were sampled using the Centre for Disease Control (CDC) light traps. A total of 110,357 adult female mosquitoes were collected. Anopheles gambiae s.l. accounted 25% of the total female mosquito collected. Relatively fewer An. funestus were collected. Other mosquito species collected were An. pharoensis, An. coustani, An. maculipalpis, An. marshallii, Culex quinquefasciatus , Cx unnivittatus, Mansonia uniformis and Ma. africana. An analysis by Polymerase Chain Reaction revealed that An. arabiensis was the only member of the An. gambiae complex in the collected samples. The number of mosquito collected correlated with the increasing mean rainfall. Blood meal analysis showed a higher human enzymatic reaction among An. gambiae s.l. (63.5%) followed by An. funestus (42.9%). Bovine enzymatic reaction was higher among An. coustani (73.7%) followed by the An. pharoensis (66.7%). The Enzyme Linked Immunosorbent Assay (ELISA) was used to detect Plasmodium falciparum circumsporozoites proteins in 10,000 female Anopheles mosquitoes. Only two An. arabiensis were found to be infected. The entomological inoculation rate (EIR) was estimated at 0.51 infectious bites per person per year. This EIR was considered to be relatively low, indicating that malaria transmission in this area is low. Variability in mosquito blood meal shows availability of variety of preferred blood meal choices and impact of other factors inhibiting mosquito-human host contact.The study has provided information considered useful in the mapping of the vector distribution and population structure in the country. Such information is considered to be among the essential tools for planning malaria control interventions

Low density parasitaemia, red blood cell polymorphisms and Plasmodium falciparum specific immune responses in a low endemic area in northern Tanzania.

BACKGROUND: Low density Plasmodium falciparum infections, below the microscopic detection limit, may play an important role in maintaining malaria transmission in low endemic areas as well as contribute to the maintenance of acquired immunity. Little is known about factors influencing the occurrence of sub-microscopic parasitaemia or the relation with immune responses.We investigated possible associations between the occurrence of sub-microscopic P. falciparum parasite carriage and antibody responses to the asexual stage antigens, G6PD deficiency and alpha+-thalassaemia in 464 subjects from a low endemic area in northern Tanzania. METHODS: We used samples collected from two cross sectional surveys conducted during dry and wet season in 2005. Submicroscopic parasitaemia was detected by using quantitative nucleic acid sequence based amplification (QT-NASBA). Genotyping for G6PD and alpha+-thalassaemia were performed by high throughput PCR; the prevalence and level of total IgG antibodies against MSP-1, MSP-2 and AMA-1 were determined by ELISA. RESULTS: Compared to parasite free individuals, individuals carrying sub-microscopic densities of P. falciparum parasites had significantly higher median antibody levels to MSP-1 (p = 0.042) and MSP-2 (p = 0.034) but not to AMA-1 (p = 0.14) while no clear relation between sub-microscopic parasite carriage and G6PD deficiency or alpha+-thalassaemia was observed. CONCLUSION: Our data suggest a role for sub-microscopic parasite densities in eliciting or maintaining humoral immune responses without evidence for a modulating effect of G6PD deficiency or alpha+-thalassaemia

Defining malaria burden from morbidity and mortality records, self treatment practices and serological data in Magugu, Babati District, northern Tanzania

Malaria morbidity and mortality data from clinical records provide essential information towards defining disease burden in the area and for planning control strategies, but should be augmented with data on transmission intensity and serological data as measures for exposure to malaria. The objective of this study was to estimate the malaria burden based on serological data and prevalence of malaria, and compare it with existing self-treatment practices in Magugu in Babati District of northern Tanzania. Prospectively, 470 individuals were selected for the study. Both microscopy and Rapid Diagnostic Test (RDT) were used for malaria diagnosis. Seroprevalence of antibodies to merozoite surface proteins (MSP- 119) and apical membrane antigen (AMA-1) was performed and the entomological inoculation rate (EIR) was estimated. To complement this information, retrospective data on treatment history, prescriptions by physicians and use of bed nets were collected. Malaria prevalence in the area was 6.8% (32/470). Of 130 individuals treated with artemisinin combination therapy (ACT), 22.3 % (29/130) were slide confirmed while 75.3% (98/130) of them were blood smear negative. Three of the slides confirmed individuals were not treated with ACT. Fever was reported in 38.2% of individuals, of whom 48.8 % (88/180) were given ACT. Forty-two (32.3%) of those who received ACT had no history of fever. About half (51.1%) of those treated with ACT were children <10 years old. Immunoglobulin against MSP-119 was positive in 16.9% (74/437) while against AMA-1 was positive in 29.8 % (130/436). Transmission intensity was estimated at <0.2 infectious bites per person per year. The RDT was highly specific (96.3%) but with low sensitivity (15.6%). In conclusion, Magugu is a low endemic area. There is substantial over diagnosis, over treatment and self treatment in the community. The burden of malaria based on medical records is over estimated as was mostly presumptive. The low sensitivity of RDT reflects the low number of immune individuals as well as the low parasite density

Prescription and non-prescription antibiotic dispensing practices in part I and part II pharmacies in Moshi Municipality, Kilimanjaro Region in Tanzania: A simulated clients approach.

Antibiotic dispensing without a prescription poses a threat to public health as it leads to excessive antibiotic consumption. Inappropriate antibiotic availability to the community has been documented to be amongst drivers of antimicrobial resistance emergence. Community pharmacies are a source of antibiotics in low and middle-income countries (LMICs). We aimed at assessing antibiotic dispensing practices by community pharmacy retailers in Moshi urban, Kilimanjaro, Tanzania and recommend interventions to improve practice. Using a Simulated Client (SC) Method, an observational cross-sectional survey of antibiotic dispensing practices was conducted from 10th June to 10th July 2017. Data analysis was done using Stata 13 (StataCorp, College Station, TX, USA). A total of 82 pharmacies were visited. Part I pharmacies were 26 (31.71%) and 56 (68.29%) were part II. Overall 92.3% (95% CI 77.8-97.6) of retailers dispensed antibiotics without prescriptions. The antibiotics most commonly dispensed without a prescription were ampiclox for cough (3 encounters) and azithromycin for painful urination (3 encounters). An oral third generation cephalosporin (cefixime) was dispensed once for painful urination without prescription by a part I pharmacy retailer. Out of 21, 15(71.43%) prescriptions with incomplete doses were accepted and had antibiotics dispensed. Out of 68, 4(5.9%) retailers gave instructions for medicine use voluntarily. None of the retailers voluntarily explained drug side-effects. In Moshi pharmacies, a high proportion of antibiotics are sold and dispensed without prescriptions. Instructions for medicine use are rarely given and none of the retailers explain side effects. These findings support the need for a legislative enforcement of prescription-only antibiotic dispensing rules and regulations. Initiation of clinician and community antibiotic stewardship and educational programs on proper antibiotic use to both pharmacists and public by the regulatory bodies are highly needed

Prevalence, determinants and knowledge of antibacterial self-medication: A cross sectional study in North-eastern Tanzania.

Self-medication is very common especially in developing countries and is documented to be associated with many health risks including antibiotic resistance. This study investigated the prevalence, determinants and knowledge of self-medication among residents of Siha District in Tanzania. A cross-sectional study was conducted among 300 residents in a rural District of Kilimanjaro region, North-eastern Tanzania from 1st to 28th April 2017. A semi-structured questionnaire was used to collect information regarding drugs used, knowledge, history and reasons for antibiotic self-medication. Log-binomial regression analysis was done using STATA 13 to examine factors associated with self-medication. A slightly majority of the respondents (58%) admitted to self-medication. Antibiotics most commonly utilized were amoxycillin (43%) and an antiprotozoal drug metronidazole (10%). The most common symptoms that led to self-medication were cough (51.17%), headache/ fever/ malaria (25.57%) and diarrhoea (21.59%). The most common reasons for self-medication were emergency illness (24.00%), health facility charges (20.33%), proximity of pharmacy to home (17.00%) and no reason (16.66%). Almost all reported that self-medication is not better than seeking medical consultation, 98% can result into harmful effects and 96% can result to drug resistance. The level of self-medication in this study is comparable with findings from other studies in developing countries. Pharmacies were commonly used as the first point of medical care. There is therefore a need for educative antibiotic legislative intervention to mitigate the adverse effects of antibiotic self-medication in Siha district in Tanzania