Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania.

Ivermectin (IVM) is a drug of choice used with albendazole for mass drug administration (MDA) to halt transmission of lymphatic filariasis. We investigated IVM pharmacokinetic (PK) variability for its dose optimization during MDA. PK samples were collected at 0, 2, 4, and 6 h from individuals weighing greater than 15 kg (n = 468) receiving IVM (3-, 6-, 9-, or 12 mg) and ALB (400 mg) during an MDA campaign in Tanzania. Individual characteristics, including demographics, laboratory/clinical parameters, and pharmacogenetic variations were assessed. IVM plasma concentrations were quantified by liquid-chromatography tandem mass spectrometry and analyzed using population-(PopPK) modeling. A two-compartment model with transit absorption kinetics, and allometrically scaled oral clearance (CL/F) and central volume (Vc /F) was adapted. Fitting of the model to the data identified 48% higher bioavailability for the 3 mg dose compared to higher doses and identified a subpopulation with 97% higher mean transit time (MTT). The final estimates for CL/F, Vc /F, intercompartment clearance, peripheral volume, MTT, and absorption rate constant for a 70 kg person (on dose other than 3 mg) were 7.7 L/h, 147 L, 20.4 L/h, 207 L, 1.5 h, and 0.71/h, respectively. Monte-Carlo simulations indicated that weight-based dosing provides comparable exposure across weight bands, but height-based dosing with capping IVM dose at 12 mg for individuals with height greater than 160 cm underdoses those weighing greater than 70 kg. Variability in IVM PKs is partly explained by body weight and dose. The established PopPK model can be used for IVM dose optimization. Height-based pole dosing results in varying IVM exposure in different weight bands, hence using weighing scales for IVM dosing during MDA is recommended.

Prevalence and Correlates of Lymphatic Filariasis Infection and Its Morbidity Following Mass Ivermectin and Albendazole Administration in Mkinga District, North-Eastern Tanzania.

Lymphatic filariasis (LF) is a neglected tropical disease targeted for elimination as public health problem through morbidity management and preventive annual mass drug administration (MDA). This cross-sectional community-based surveillance assessed the prevalence and correlates of LF infection in Mkinga district, Tanga-region, Tanzania. A total of 4115 individuals (49.7% males, 35.2% children) were screened for circulating filarial antigens (CFA), microfilaremia (mf) and disease manifestations in 15 villages between November 2018 and January 2019. MDA uptake in the previous year was assessed. Overall prevalence of CFA-positivity was 5.8% (239/4115; 95% CI: 5.1-6.6), with significant heterogeneity between villages (range 1.2% to 13.5%). CFA-positivity was higher in males (8.8%) than females (3.3%), and correlated with increasing age (p < 0.001). Prevalence of mf among CFA-positives was 5.2%. Only 60% of eligible inhabitants in the study area took MDA in the previous year, and CFA-positivity was 2-fold higher in those who missed MDA (p < 0.0001). Prevalence of scrotal enlargement, hydrocele, arms or legs swelling, lymphoedema and lymphadenopathy was 6.4%, 3.7%, 1.35%, 1.2% and 0.32%, respectively. Compared to baseline data, 16 years of MDA intervention significantly reduced LF transmission and morbidity, although the intended elimination target of <1% mf and <2% antigenemia to level where recrudescence is unlikely to occur by the year 2020 may not be attained. The finding of hotspots with ongoing transmission calls for intensified control measures.

Lymphatic filariasis patient identification in a large urban area of Tanzania: An application of a community-led mHealth system.

BACKGROUND: Lymphatic filariasis (LF) is best known for the disabling and disfiguring clinical conditions that infected patients can develop; providing care for these individuals is a major goal of the Global Programme to Eliminate LF. Methods of locating these patients, knowing their true number and thus providing care for them, remains a challenge for national medical systems, particularly when the endemic zone is a large urban area. METHODOLOGY/PRINCIPLE FINDINGS: A health community-led door-to-door survey approach using the SMS reporting tool MeasureSMS-Morbidity was used to rapidly collate and monitor data on LF patients in real-time (location, sex, age, clinical condition) in Dar es Salaam, Tanzania. Each stage of the phased study carried out in the three urban districts of city consisted of a training period, a patient identification and reporting period, and a data verification period, with refinements to the system being made after each phase. A total of 6889 patients were reported (133.6 per 100,000 population), of which 4169 were reported to have hydrocoele (80.9 per 100,000), 2251 lymphoedema-elephantiasis (LE) (43.7 per 100,000) and 469 with both conditions (9.1 per 100,000). Kinondoni had the highest number of reported patients in absolute terms (2846, 138.9 per 100,000), followed by Temeke (2550, 157.3 per 100,000) and Ilala (1493, 100.5 per 100,000). The number of hydrocoele patients was almost twice that of LE in all three districts. Severe LE patients accounted for approximately a quarter (26.9%) of those reported, with the number of acute attacks increasing with reported LE severity (1.34 in mild cases, 1.78 in moderate cases, 2.52 in severe). Verification checks supported these findings. CONCLUSIONS/SIGNIFICANCE: This system of identifying, recording and mapping patients affected by LF greatly assists in planning, locating and prioritising, as well as initiating, appropriate morbidity management and disability prevention (MMDP) activities. The approach is a feasible framework that could be used in other large urban environments in the LF endemic areas.

Fine scale mapping of malaria infection clusters by using routinely collected health facility data in urban Dar es Salaam, Tanzania.

This study investigated whether passively collected routine health facility data can be used for mapping spatial heterogeneities in malaria transmission at the level of local government housing cluster administrative units in Dar es Salaam, Tanzania. From June 2012 to January 2013, residential locations of patients tested for malaria at a public health facility were traced based on their local leaders' names and geo-referencing the point locations of these leaders' houses. Geographic information systems (GIS) were used to visualise the spatial distribution of malaria infection rates. Spatial scan statistics was deployed to detect spatial clustering of high infection rates. Among 2407 patients tested for malaria, 46.6% (1121) could be traced to their 411 different residential housing clusters. One small spatially aggregated cluster of neighbourhoods with high prevalence was identified. While the home residence housing cluster leader was unambiguously identified for 73.8% (240/325) of malaria-positive patients, only 42.3% (881/2082) of those with negative test results were successfully traced. It was concluded that recording simple points of reference during routine health facility visits can be used for mapping malaria infection burden on very fine geographic scales, potentially offering a feasible approach to rational geographic targeting of malaria control interventions. However, in order to tap the full potential of this approach, it would be necessary to optimise patient tracing success and eliminate biases by blinding personnel to test results.

Mobile Phones As Surveillance Tools: Implementing and Evaluating a Large-Scale Intersectoral Surveillance System for Rabies in Tanzania.

Katie Hampson and colleagues describe their experience of developing and deploying a large-scale rabies surveillance system based on mobile phones in southern Tanzania.

A generic schema and data collection forms applicable to diverse entomological studies of mosquitoes.

BACKGROUND: Standardized schemas, databases, and public data repositories are needed for the studies of malaria vectors that encompass a remarkably diverse array of designs and rapidly generate large data volumes, often in resource-limited tropical settings lacking specialized software or informatics support. RESULTS: Data from the majority of mosquito studies conformed to a generic schema, with data collection forms recording the experimental design, sorting of collections, details of sample pooling or subdivision, and additional observations. Generically applicable forms with standardized attribute definitions enabled rigorous, consistent data and sample management with generic software and minimal expertise. Forms use now includes 20 experiments, 8 projects, and 15 users at 3 research and control institutes in 3 African countries, resulting in 11 peer-reviewed publications. CONCLUSION: We have designed generic data schema that can be used to develop paper or electronic based data collection forms depending on the availability of resources. We have developed paper-based data collection forms that can be used to collect data from majority of entomological studies across multiple study areas using standardized data formats. Data recorded on these forms with standardized formats can be entered and linked with any relational database software. These informatics tools are recommended because they ensure that medical entomologists save time, improve data quality, and data collected and shared across multiple studies is in standardized formats hence increasing research outputs.

PGMS: a case study of collecting PDA-based geo-tagged malaria-related survey data.

Using mobile devices, such as personal digital assistants (PDAs), smartphones, tablet computers, etc., to electronically collect malaria-related field data is the way for the field questionnaires in the future. This case study seeks to design a generic survey framework PDA-based geo-tagged malaria-related data collection tool (PGMS) that can be used not only for large-scale community-level geo-tagged electronic malaria-related surveys, but also for a wide variety of electronic data collections of other infectious diseases. The framework includes two parts: the database designed for subsequent cross-sectional data analysis and the customized programs for the six study sites (two in Kenya, three in Indonesia, and one in Tanzania). In addition to the framework development, we also present our methods used when configuring and deploying the PDAs to 1) reduce data entry errors, 2) conserve battery power, 3) field install the programs onto dozens of handheld devices, 4) translate electronic questionnaires into local languages, 5) prevent data loss, and 6) transfer data from PDAs to computers for future analysis and storage. Since 2008, PGMS has successfully accomplished quite a few surveys that recorded 10,871 compounds and households, 52,126 persons, and 17,100 bed nets from the six sites. These numbers are still growing.

An affordable, quality-assured community-based system for high-resolution entomological surveillance of vector mosquitoes that reflects human malaria infection risk patterns.

BACKGROUND: More sensitive and scalable entomological surveillance tools are required to monitor low levels of transmission that are increasingly common across the tropics, particularly where vector control has been successful. A large-scale larviciding programme in urban Dar es Salaam, Tanzania is supported by a community-based (CB) system for trapping adult mosquito densities to monitor programme performance. METHODOLOGY: An intensive and extensive CB system for routine, longitudinal, programmatic surveillance of malaria vectors and other mosquitoes using the Ifakara Tent Trap (ITT-C) was developed in Urban Dar es Salaam, Tanzania, and validated by comparison with quality assurance (QA) surveys using either ITT-C or human landing catches (HLC), as well as a cross-sectional survey of malaria parasite prevalence in the same housing compounds. RESULTS: Community-based ITT-C had much lower sensitivity per person-night of sampling than HLC (Relative Rate (RR) [95% Confidence Interval (CI)] = 0.079 [0.051, 0.121], P < 0.001 for Anopheles gambiae s.l. and 0.153 [0.137, 0.171], P < 0.001 for Culicines) but only moderately differed from QA surveys with the same trap (0.536 [0.406,0.617], P = 0.001 and 0.747 [0.677,0.824], P < 0.001, for An. gambiae or Culex respectively). Despite the poor sensitivity of the ITT per night of sampling, when CB-ITT was compared with QA-HLC, it proved at least comparably sensitive in absolute terms (171 versus 169 primary vectors caught) and cost-effective (153US$ versus 187US$ per An. gambiae caught) because it allowed more spatially extensive and temporally intensive sampling (4284 versus 335 trap nights distributed over 615 versus 240 locations with a mean number of samples per year of 143 versus 141). Despite the very low vectors densities (Annual estimate of about 170 An gambiae s.l bites per person per year), CB-ITT was the only entomological predictor of parasite infection risk (Odds Ratio [95% CI] = 4.43[3.027,7. 454] per An. gambiae or Anopheles funestus caught per night, P =0.0373). DISCUSSION AND CONCLUSION: CB trapping approaches could be improved with more sensitive traps, but already offer a practical, safe and affordable system for routine programmatic mosquito surveillance and clusters could be distributed across entire countries by adapting the sample submission and quality assurance procedures accordingly.