Evaluation of Targeted Mass Drug Administration for Malaria in Ethiopia

Malaria burden, measured by antigen test

Testing for pan-Plasmodium antigens aldolase and LDH will determine active infection with malaria parasite, and, if the infecting species is Pf, by the presence of HRP2 antigen (Plucinski, Herman et al. 2018).

Time frame: Two years

Malaria burden, measured by serology

Sero-prevalence will be determined using LUMINEX based multiplex assays. Age-specific sero-conversion and sero-reversion rates over the two years will be used to monitor changes in transmission and malaria exposure over time. Absence of antimalarial antibodies, particularly in children, will show the success of tMDA or RCD interventions. Antigen selection will be informed by recent studies by EPHI and CDC and a panel of antibodies characterized to indicate recent change in transmission will be included (Kerkhof, Sluydts et al. 2016).

Time frame: Two years

Malaria burden, measured by molecular testing

Real-time quantitative (qPCR) for parasite detection will be performed by targeting the 18S small rRNA gene for Pf and Pv using primer and probe sequences. Pf parasites will be quantified using standard curves generated from a serial dilution of NF54 ring stage parasites. Pv parasite quantification will be done using plasmid constructs to infer copy numbers as described before. Blood samples in RNA protect buffers will be used for extraction of RNA using the RNeasy Mini Kit (QIAGEN) for gametocyte quantification, gametocyte commitment and maturation assays, sex ratio estimation, asexual stage parasites detection, and expression level of regulators of the balance between reproduction and replication.

Time frame: Two years

Intervention coverage

To compare intervention coverage in RCD and tMDA arms. After RCD and tMDA interventions, coverage will be estimated by calculating the proportion of all enumerated household members reached in each index case event and the proportion of individuals tested and/or on treatment.

Time frame: Two years

Acceptability

To compare acceptability of RCD and tMDA. During the baseline and endline cross-sectional surveys, the household head will be asked questions about the acceptability of the RCD and tMDA interventions (self-report).

Time frame: Two years

Serious adverse events

To compare number of serious adverse events between the RCD and tMDA arms

Time frame: Two years

Adherence

To compare the adherence to antimalarials between the RCD and tMDA arms. Adherence will be measured by self-report and pill count.

Time frame: Two years

Costs

To compare the costs of RCD and tMDA. Costs will be calculated using an ingredients approach that involves enumerating both the quantity of specific inputs (e.g., hours spent, cost of treatment, number of RDTs used, etc.) and the time spent during the intervention. Quantity and time will be converted to a common monetary cost measure. Existing infrastructure and recurrent inputs that would be present in the absence of the intervention will not be included in cost analysis. The emphasis of the cost analysis is on determining the cost of RCD and tMDA alone.

Time frame: Two years

Cost-effectiveness

To assess the cost-effectiveness of RCD and tMDA relative to control. Cost-effectiveness will be measured through incident malaria cases averted as measured through the difference in malaria incidence in RCD and tMDA kebeles.

Time frame: Two years

Sensitivity and specificity of polymerase chain reaction (PCR)

To evaluate the sensitivity and specificity of PCR as compared to antigen- based multiplex testing

Time frame: Two years

Ratio of imported to locally acquired incident cases

To assess the ratio of imported to locally acquired incident cases

Time frame: Two years