Evaluation of Malaria Rapid Diagnostic Test Performance and pfhrp2 Deletion in Tanzania School Surveys, 2017.

As part of malaria nationwide monitoring and evaluation initiatives, there is an increasing trend of incorporating malaria rapid diagnostic tests (mRDTs) in surveys conducted within primary schools to detect malaria parasites. However, mRDTs based on the detection of histidine-rich protein 2 (HRP2) are known to yield false-positive results due to persistent antigenemia, and false-negative results may result from low parasitemia or Plasmodium falciparum hrp2/3 gene deletion. We evaluated diagnostic performance of an HRP2 and pan-parasite lactate dehydrogenase (HRP2/pLDH) mRDT against polymerase chain reaction (PCR) for detection of P. falciparum among 17,051 primary school-age children from eight regions of Tanzania in 2017. According to PCR, the prevalence of P. falciparum was 19.2% (95% CI: 18.6-19.8). Using PCR as reference, the sensitivity and specificity of mRDT was 76.2% (95% CI: 74.7-77.7) and 93.9% (95% CI: 93.5-94.3), respectively. Test agreement was lowest in low transmission areas, where true-positive mRDTs were outnumbered by false-negatives due to low parasitemia. Discordant samples (mRDT-negative but PCR-positive) were screened for pfhrp2/3 deletion by real-time PCR. Among those with a parasite density sufficient for analysis, pfhrp2 deletion was confirmed in 60 samples, whereas pfhrp3 deletion was confirmed in two samples; one sample had both pfhrp2 and pfhrp3 deletions. The majority of samples with gene deletions were detected in the high-transmission Kagera region. Compared with mRDTs, PCR and other molecular methods offer increased sensitivity and are not affected by pfhrp2/3 deletions, making them a useful supplement to mRDTs in schools and other epidemiological surveys.

How Real-Time Case-Based Malaria Surveillance Helps Zanzibar Get a Step Closer to Malaria Elimination: Description of Operational Platform and Resources.

Testing and treating asymptomatic populations have the potential to reduce the population's parasite reservoir and reduce malaria transmission. Zanzibar's malaria case notification (MCN) platform collects detailed sociodemographic and epidemiological data from all confirmed malaria cases to inform programmatic decision-making. We describe the design and operationalization process of the platform and other malaria surveillance resources that are enabling Zanzibar's progress toward malaria elimination.The MCN platform consists of an interactive short message service (SMS) system for case notification, a software application for Android mobile devices, a visual question set and workflow manager, a back-end database server, and a web browser-based application for data analytics, configuration, and management. Malaria case data were collected from August 2012 to December 2021 and reported via SMS from all public and private health facilities to a central database and then to district malaria surveillance officers' mobile devices. Data included patient names, shehia (administrative area), and date of diagnosis, enabling officers to track patients, ideally within 24 hours of reporting. Patients' household members were tested for malaria using conventional rapid diagnostic tests (RDTs). Treatment using artemisinin-based combination therapy was provided for persons testing positive.Between 2012 and 2021, a total of 48,899 index malaria cases were confirmed at health facilities, 22,152 (45.3%) within 24 hours of reporting; 41,886 (85.7%) cases were fully investigated and followed up to the household level. A total of 111,811 additional household members were tested with RDTs, of whom 10,602 (9.5%) were malaria positive.The MCN platform reports malaria case data in near real time, enabling prompt follow-up of index cases and prompt testing and treatment of members in index case households. Along with routine testing and treatment and other preventive interventions, the MCN platform is foundational to the programmatic efforts in further reducing malaria and ultimately eliminating autochthonous malaria transmission in Zanzibar.

Malaria elimination in Zanzibar: where next?

In 2018, Zanzibar developed a national malaria strategic plan IV (2018-2023) to guide elimination of malaria by 2023. We assessed progress in the implementation of malaria activities as part of the end-term review of the strategic plan. The review was done between August and October 2022 following the WHO guideline to assess progress made towards malaria elimination, effectiveness of the health systems in delivering malaria case management; and malaria financing. A desk review examined available malaria data, annual work plans and implementation reports for evidence of implemented malaria activities. This was complemented by field visits to selected health facilities and communities by external experts, and interviews with health management teams and inhabitants to authenticate desk review findings. A steady increase in the annual parasite incidence (API) was observed in Zanzibar, from 2.7 (2017) to 3.6 (2021) cases per 1,000 population with marked heterogeneity between areas. However, about 68% of the detected malaria cases were imported into Zanzibar. Malaria case follow-up and investigation increased from <70% in 2017 to 94% and 96% respectively, in 2021. The review noted a 3.7-fold increase of the health allocation in the country's budget, from 31.7 million USD (2017/18) to 117.3 million USD (2022/23) but malaria allocation remained low (<1%). The varying transmission levels in the islands suggest a need for strategic re-orientation of the elimination attempts from a national-wide to a sub-national agenda. We recommend increasing malaria allocation from the health budget to ensure sustainability of malaria elimination interventions.

Similar Prevalence of Plasmodium falciparum and Non-P. falciparum Malaria Infections among Schoolchildren, Tanzania1.

Achieving malaria elimination requires considering both Plasmodium falciparum and non-P. falciparum infections. We determined prevalence and geographic distribution of 4 Plasmodium spp. by performing PCR on dried blood spots collected within 8 regions of Tanzania during 2017. Among 3,456 schoolchildren, 22% had P. falciparum, 24% had P. ovale spp., 4% had P. malariae, and 0.3% had P. vivax infections. Most (91%) schoolchildren with P. ovale infections had low parasite densities; 64% of P. ovale infections were single-species infections, and 35% of those were detected in low malaria endemic regions. P. malariae infections were predominantly (73%) co-infections with P. falciparum. P. vivax was detected mostly in northern and eastern regions. Co-infections with >1 non-P. falciparum species occurred in 43% of P. falciparum infections. A high prevalence of P. ovale infections exists among schoolchildren in Tanzania, underscoring the need for detection and treatment strategies that target non-P. falciparum species.

Trends of insecticide resistance monitoring in mainland Tanzania, 2004-2020.

BACKGROUND: Insecticide resistance is a serious threat to the continued effectiveness of insecticide-based malaria vector control measures, such as long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS). This paper describes trends and dynamics of insecticide resistance and its underlying mechanisms from annual resistance monitoring surveys on Anopheles gambiae sensu lato (s.l.) populations conducted across mainland Tanzania from 2004 to 2020. METHODS: The World Health Organization (WHO) standard protocols were used to assess susceptibility of the wild female An. gambiae s.l. mosquitoes to insecticides, with mosquitoes exposed to diagnostic concentrations of permethrin, deltamethrin, lambdacyhalothrin, bendiocarb, and pirimiphos-methyl. WHO test papers at 5× and 10× the diagnostic concentrations were used to assess the intensity of resistance to pyrethroids; synergist tests using piperonyl butoxide (PBO) were carried out in sites where mosquitoes were found to be resistant to pyrethroids. To estimate insecticide resistance trends from 2004 to 2020, percentage mortalities from each site and time point were aggregated and regression analysis of mortality versus the Julian dates of bioassays was performed. RESULTS: Percentage of sites with pyrethroid resistance increased from 0% in 2004 to more than 80% in the 2020, suggesting resistance has been spreading geographically. Results indicate a strong negative association (p = 0.0001) between pyrethroids susceptibility status and survey year. The regression model shows that by 2020 over 40% of An. gambiae mosquitoes survived exposure to pyrethroids at their respective diagnostic doses. A decreasing trend of An. gambiae susceptibility to bendiocarb was observed over time, but this was not statistically significant (p = 0.8413). Anopheles gambiae exhibited high level of susceptibility to the pirimiphos-methyl in sampled sites. CONCLUSIONS: Anopheles gambiae Tanzania's major malaria vector, is now resistant to pyrethroids across the country with resistance increasing in prevalence and intensity and has been spreading geographically. This calls for urgent action for efficient malaria vector control tools to sustain the gains obtained in malaria control. Strengthening insecticide resistance monitoring is important for its management through evidence generation for effective malaria vector control decision.

Spatiotemporal dynamics of malaria in Zanzibar, 2015-2020.

BACKGROUND: Despite high coverage of malaria interventions, malaria elimination in Zanzibar remains elusive, with the annual number of cases increasing gradually over the last 3 years. OBJECTIVE: The aims of the study were to (1) assess the spatiotemporal dynamics of malaria in Zanzibar between 2015 and 2020 and (2) identify malaria hotspots that would allow Zanzibar to develop an epidemiological stratification for more effective and granular intervention targeting. METHODS: In this study, we analysed data routinely collected by Zanzibar's Malaria Case Notification (MCN) system. The system collects sociodemographic and epidemiological data from all malaria cases. Cases are passively detected at health facilities (ie, primary index cases) and through case follow-up and reactive case detection (ie, secondary cases). Analyses were performed to identify the spatial heterogeneity of case reporting at shehia (ward) level during transmission seasons. RESULTS: From 1 January 2015 to 30 April 2020, the MCN system reported 22 686 index cases. Number of cases reported showed a declining trends from 2015 to 2016, followed by an increase from 2017 to 2020. More than 40% of cases had a travel history outside Zanzibar in the month prior to testing positive for malaria. The proportion of followed up index cases was approximately 70% for all years. Out of 387 shehias, 79 (20.4%) were identified as malaria hotspots in any given year; these hotspots reported 52% of all index cases during the study period. Of the 79 hotspot shehias, 12 were hotspots in more than 4 years, that is, considered temporally stable, reporting 14.5% of all index cases. CONCLUSIONS: Our findings confirm that the scale-up of malaria interventions has greatly reduced malaria transmission in Zanzibar since 2006. Analyses identified hotspots, some of which were stable across multiple years. Malaria efforts should progress from a universal intervention coverage approach to an approach that is more tailored to a select number of hotspot shehias.

Improvements in malaria surveillance through the electronic Integrated Disease Surveillance and Response (eIDSR) system in mainland Tanzania, 2013-2021.

BACKGROUND: Tanzania has made remarkable progress in reducing malaria burden and aims to transition from malaria control to sub-national elimination. In 2013, electronic weekly and monthly reporting platforms using the District Health Information System 2 (DHIS2) were introduced. Weekly reporting was implemented through the mobile phone-based Integrated Disease Surveillance and Response (eIDSR) platform and progressively scaled-up from 67 to 7471 (100%) public and private health facilities between 2013 and 2020. This study describes the roll-out and large-scale implementation of eIDSR and compares the consistency between weekly eIDSR and monthly DHIS2 malaria indicator data reporting, including an assessment of its usefulness for malaria outbreak detection and case-based surveillance (CBS) in low transmission areas. METHODS: The indicators included in the analysis were number of patients tested for malaria, number of confirmed malaria cases, and clinical cases (treated presumptively for malaria). The analysis described the time trends of reporting, testing, test positivity, and malaria cases between 2013 and 2021. For both weekly eIDSR and monthly DHIS2 data, comparisons of annual reporting completeness, malaria cases and annualized incidence were performed for 2020 and 2021; additionally, comparisons were stratified by malaria epidemiological strata (parasite prevalence: very low < 1%, low 1 ≤ 5%, moderate 5 ≤ 30%, and high > 30%). RESULTS: Weekly eIDSR reporting completeness steadily improved over time, with completeness being 90.2% in 2020 and 93.9% in 2021; conversely, monthly DHIS2 reporting completeness was 98.9% and 98.7% in 2020 and 2021, respectively. Weekly eIDSR reporting completeness and timeliness were highest in the very low epidemiological stratum. Annualized malaria incidence as reported by weekly eIDSR was 17.5% and 12.4% lower than reported by monthly DHIS2 in 2020 and 2021; for both 2020 and 2021, annualized incidence was similar across weekly and monthly data in the very low stratum. CONCLUSION: The concurrence of annualized weekly eIDSR and monthly DHIS2 reporting completeness, malaria cases and incidence in very low strata suggests that eIDSR could be useful tool for early outbreak detection, and the eIDSR platform could reliably be expanded by adding more indicators and modules for CBS in the very low epidemiological stratum.

Evaluating malaria prevalence and land cover across varying transmission intensity in Tanzania using a cross-sectional survey of school-aged children.

BACKGROUND: Transmission of malaria in sub-Saharan Africa has become increasingly stratified following decades of malaria control interventions. The extent to which environmental and land cover risk factors for malaria may differ across distinct strata of transmission intensity is not well known and could provide actionable targets to maximize the success of malaria control efforts. METHODS: This study used cross-sectional malaria survey data from a nationally representative cohort of school-aged children in Tanzania, and satellite-derived measures for environmental features and land cover. Hierarchical logistic regression models were applied to evaluate associations between land cover and malaria prevalence within three distinct strata of transmission intensity: low and unstable, moderate and seasonal, and high and perennial. RESULTS: In areas with low malaria transmission, each 10-percentage point increase in cropland cover was associated with an increase in malaria prevalence odds of 2.44 (95% UI: 1.27, 5.11). However, at moderate and higher levels of transmission intensity, no association between cropland cover and malaria prevalence was detected. Small associations were observed between greater grassland cover and greater malaria prevalence in high intensity settings (prevalence odds ratio (POR): 1.10, 95% UI: 1.00, 1.21), and between greater forest cover and reduced malaria prevalence in low transmission areas (POR: 0.74, 95% UI: 0.51, 1.03), however the uncertainty intervals of both estimates included the null. CONCLUSIONS: The intensity of malaria transmission appears to modify relationships between land cover and malaria prevalence among school-aged children in Tanzania. In particular, greater cropland cover was positively associated with increased malaria prevalence in areas with low transmission intensity and presents an actionable target for environmental vector control interventions to complement current malaria control activities. As areas are nearing malaria elimination, it is important to re-evaluate environmental risk factors and employ appropriate interventions to effectively address low-level malaria transmission.

Factors associated with community engagement in areas with high and low incidence of local malaria cases in Zanzibar

Introduction: the prevalence of asymptomatic infection in the general population in Zanzibar has declined from above 25% in 2005 to less than 1% in 2010. Despite these achievements, in 2021, the number of malaria cases increased by two folds. This study aimed at understanding the levels of community engagement towards malaria elimination and factors associated with them to provide recommendations that can be used to reinforce community engagement. Methods: a descriptive cross-sectional survey was conducted using structured questionnaires to 431 randomly selected households. The interviewees were the heads of households or representative adults above 18 years. Univariate and multivariate analysis was done to determine the association between social demographic characteristics, malaria knowledge, practicing malaria prevention interventions and status of community engagement. Statistical significance test was declared at P- value <0.05. Results: of all respondents, 261 (60.6%) were not engaged in either planning or implementation of malaria interventions, of which 120 (45.9%) participants were in the high malaria transmission and 141 (54.0%) from the low malaria transmission (P=0.018). Factors significantly associated with increased odds of community engagement were the level of knowledge on malaria (P= 0.002) and factors independently associated with reduced odds of community engagement was the level of malaria burden (P= 0.01). Conclusion: level of malaria knowledge and malaria burden were associated with community engagement. There is a need to increase malaria knowledge in the community based on the existing gaps as this study suggests that having high malaria knowledge can significantly contribute to increased opportunity for community engagement.

Risk factors associated with malaria infection identified through reactive case detection in Zanzibar, 2012-2019.

BACKGROUND: Over the past two decades, Zanzibar substantially reduced malaria burden. As malaria decreases, sustainable improvements in control interventions may increasingly depend on accurate knowledge of malaria risk factors to further target interventions. This study aimed to investigate the risk factors associated with malaria infection in Zanzibar. METHODS: Surveillance data from Zanzibar's Malaria Case Notification system from August 2012 and December 2019 were analyzed. This system collects data on malaria cases passively detected and reported by all health facilities (index cases), and household-based reactive case detection (RCD) activities linked to those primary cases. All members of households of the index cases were screened for malaria using a malaria rapid diagnostic test (RDT). Individuals with a positive RDT were treated with artemisinin-based combination therapy. Univariate and multivariate logistic regression analyses were done to investigate the association between RDT positivity among the household members and explanatory factors with adjustment for seasonality and clustering at Shehia level. RESULTS: A total of 30,647 cases were reported of whom household RCD was completed for 21,443 (63%) index case households and 85,318 household members tested for malaria. The findings show that younger age (p-value for trend [Ptrend] < 0.001), history of fever in the last 2 weeks (odds ratio [OR] = 35.7; 95% CI 32.3-39.5), travel outside Zanzibar in the last 30 days (OR = 2.5; 95% CI 2.3-2.8) and living in Unguja (OR = 1.2; 95% CI 1.0-1.5) were independently associated with increased odds of RDT positivity. In contrast, male gender (OR=0.8; 95% CI 0.7-0.9), sleeping under an LLIN the previous night (OR = 0.9; 95% CI 0.7-0.9), having higher household net access (Ptrend < 0.001), and living in a household that received IRS in the last 12 months (OR = 0.8; 95% CI 0.7-0.9) were independently associated with reduced odds of RDT positivity. A significant effect modification of combining IRS and LLIN was also noted (OR = 0.7; 95% CI 0.6-0.8). CONCLUSIONS: The findings suggest that vector control remains an important malaria prevention intervention: they underscore the need to maintain universal access to LLINs, the persistent promotion of LLIN use, and application of IRS. Additionally, enhanced behavioural change and preventive strategies targeting children aged 5-14 years and travellers are needed.

Evaluating Response Time in Zanzibar's Malaria Elimination Case-Based Surveillance-Response System.

As countries transition toward malaria elimination, malaria programs rely on surveillance-response systems, which are often supported by web- and mobile phone-based reporting tools. Such surveillance-response systems are interventions for elimination, making it important to determine if they are operating optimally. A metric to measure this by is timeliness. This study used a mixed-methods approach to investigate the response time of Zanzibar's malaria elimination surveillance-response system, Malaria Case Notification (MCN). MCN conducts both passive and reactive case detection, supported by a mobile phone-based reporting tool called Coconut Surveillance. Using data obtained from RTI International and the Zanzibar Malaria Elimination Program (ZAMEP), analysis of summary statistics was conducted to investigate the association of response time with geography, and time series techniques were used to investigate trends in response time and its association with the number of reported cases. Results indicated that response time varied by the district in Zanzibar (0.6-6.05 days) and that it was not associated with calendar time or the number of reported cases. Survey responses and focus groups with a cadre of health workers, district malaria surveillance officers, shed light on operational challenges faced during case investigation, such as incomplete health records and transportation issues, which stem from deficiencies in aspects of ZAMEP's program management. These findings illustrate that timely response for malaria elimination depends on effective program management, despite the automation of web-based or mobile phone-based tools. For surveillance-response systems to work optimally, malaria programs should ensure that optimal management practices are in place.

A cluster randomised controlled trial of two rounds of mass drug administration in Zanzibar, a malaria pre-elimination setting-high coverage and safety, but no significant impact on transmission.

BACKGROUND: Mass drug administration (MDA) has the potential to interrupt malaria transmission and has been suggested as a tool for malaria elimination in low-endemic settings. This study aimed to determine the effectiveness and safety of two rounds of MDA in Zanzibar, a pre-elimination setting. METHODS: A cluster randomised controlled trial was conducted in 16 areas considered as malaria hotspots, with an annual parasite index of > 0.8%. The areas were randomised to eight intervention and eight control clusters. The intervention included two rounds of MDA with dihydroartemisinin-piperaquine and single low-dose primaquine 4 weeks apart in May-June 2016. Primary and secondary outcomes were cumulative confirmed malaria case incidences 6 months post-MDA and parasite prevalences determined by PCR 3 months post-MDA. Additional outcomes included intervention coverage, treatment adherence, occurrence of adverse events, and cumulative incidences 3, 12, and 16 months post-MDA. RESULTS: Intervention coverage was 91.0% (9959/10944) and 87.7% (9355/10666) in the first and second rounds, respectively; self-reported adherence was 82.0% (881/1136) and 93.7% (985/1196). Adverse events were reported in 11.6% (147/1268) and 3.2% (37/1143) of post-MDA survey respondents after both rounds respectively. No serious adverse event was reported. No difference in cumulative malaria case incidence was observed between the control and intervention arms 6 months post-MDA (4.2 and 3.9 per 1000 population; p = 0.94). Neither was there a difference in PCR-determined parasite prevalences 3 months post-MDA (1.4% and 1.7%; OR = 1.0, p = 0.94), although having received at least the first MDA was associated with reduced odds of malaria infection (aOR = 0.35; p = 0.02). Among confirmed malaria cases at health facilities, 26.0% and 26.3% reported recent travel outside Zanzibar in the intervention and control shehias (aOR ≥ 85; p ≤ 0.001). CONCLUSIONS: MDA was implemented with high coverage, adherence, and tolerability. Despite this, no significant impact on transmission was observed. The findings suggest that two rounds of MDA in a single year may not be sufficient for a sustained impact on transmission in a pre-elimination setting, especially when the MDA impact is restricted by imported malaria. Importantly, this study adds to the limited evidence for the use of MDA in low transmission settings in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02721186 (registration date: March 29, 2016).

Artemisinin combination therapy mass drug administration in a setting of low malaria endemicity: programmatic coverage and adherence during an observational study in Zanzibar.

BACKGROUND: Mass drug administration (MDA) appears to be effective in reducing the risk of malaria parasitaemia. This study reports on programmatic coverage and compliance of MDA using artemisinin-based combination therapy (ACT) in four shehias (smallest administration unit) that had been identified as hotspots through Zanzibar's malaria case notification surveillance system. METHODS: Mass drug administration was done in four shehias selected on the basis of: being an established malaria hot spot; having had mass screening and treatment (MSaT) 2-6 weeks previously; and exceeding the epidemic alert threshold of 5 cases within a week even after MSaT. Communities were sensitized and MDA was conducted using a house-to-house approach. All household members, except pregnant women and children aged less than 2 months, were provided with ACT medicine. Two weeks after the MDA campaign, a survey was undertaken to investigate completion of ACT doses. RESULTS: A total of 8816 [97.1% of eligible; 95% confidence interval (CI) 96.8-97.5] people received ACT. During post MDA surveys, 2009 people were interviewed: 90.2% reported having completed MDA doses; 1.9% started treatment but did not complete dosage; 4.7% did not take treatment; 2.0% were absent during MDA and 1.2% were ineligible (i.e. infants <2 months and pregnant women). Main reasons for failure to complete treatment were experience of side-effects and forgetting to take subsequent doses. Failure to take treatment was mainly due to fear of side-effects, reluctance due to lack of malaria symptoms and caregivers forgetting to give medication to children. CONCLUSION: Mass drug administration for malaria was well accepted by communities at high risk of malaria in Zanzibar, with high participation and completion rates. Further work to investigate the potential of MDA in accelerating Zanzibar's efforts towards malaria elimination should be pursued.

Progress of Trachoma Mapping in Mainland Tanzania: Results of Baseline Surveys from 2012 to 2014.

PURPOSE: Following surveys in 2004-2006 in 50 high-risk districts of mainland Tanzania, trachoma was still suspected to be widespread elsewhere. We report on baseline surveys undertaken from 2012 to 2014. METHODS: A total of 31 districts were surveyed. In 2012 and 2013, 12 at-risk districts were selected based on proximity to known trachoma endemic districts, while in 2014, trachoma rapid assessments were undertaken, and 19 of 55 districts prioritized for baseline surveys. A multi-stage cluster random sampling methodology was applied whereby 20 villages (clusters) and 36 households per cluster were surveyed. Eligible participants, children aged 1-9 years and people aged 15 years and older, were examined for trachoma using the World Health Organization simplified grading system. RESULTS: A total of 23,171 households were surveyed and 104,959 participants (92.3% of those enumerated) examined for trachoma signs. A total of 44,511 children aged 1-9 years and 65,255 people aged 15 years and older were examined for trachomatous inflammation-follicular (TF) and trichiasis, respectively. Prevalence of TF varied by district, ranging from 0.0% (95% confidence interval, CI 0.0-0.1%) in Mbinga to 11.8% (95% CI 6.8-16.5%) in Chunya. Trichiasis prevalence was lowest in Urambo (0.03%, 95% CI 0.00-0.24%) and highest in Kibaha (1.08%, 95% CI 0.74-1.43%). CONCLUSION: Only three districts qualified for mass drug administration with azithromycin. Trichiasis is still a public health problem in many districts, thus community-based trichiasis surgery should be considered to prevent blindness due to trachoma. These findings will facilitate achievement of trachoma elimination objectives.

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-1(19)) 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.

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.1. 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.1. (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.

Child hospitalization due to severe malaria is associated with the ICAM-1Kilifi allele but not adherence patterns of Plasmodium falciparum infected red blood cells to ICAM-1.

This study aimed at determining whether the predisposition of a mutation at position 179 of the ICAM-1 gene to child hospitalization due to malaria was mediated by changes in adherence properties of IRBCs to ICAM-1. ICAM-1 genotypes were determined by nested polymerase chain reaction of isolated DNA from filter blood spots followed by Restriction Fragment Length Polymorphism (RFLP). Plasmodium falciparum adherence assays were done on immobilized purified ICAM-1. Our data indicate that the homozygosity for the ICAM-1(Kilifi) mutation occurs at a frequency of 22.3% in Magugu-Babati, Northern Tanzania. Our results show that there are no differences in IRBC binding profiles across genotypes. We show in this study that homozygosity for the ICAM-1(Kilifi) is associated with child hospitalization (X(2)=14.47, p<0.001). We have further shown that hospitalization was not associated with cytoadherence (X(2)=0.17, p=0.68). We conclude that the ICAM-1(Kilifi) allele occurs at a high frequency in Tanzania and that associations of this allele with higher child hospitalization frequencies is independent of cytoadherence patterns of IRBC isolated from ICAM-1 genotypes, implying that any associations reported to exist between the ICAM-1(Kilifi) mutation and severe malaria are unlikely to be mediated through altered IRBC cytoadherence properties.

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.