Malaria programs should ensure early diagnosis and appropriate treatment (EDAT) of all clinical malaria cases in line with national treatment guidelines. This entails expanding access as well as availability and quality. Both the availability and quality of passive case detection and treatment by health facilities, community workers and private providers are improved through clinical and management (supply management, reporting) capacity building, supervision, and increased coordination with other sub-national providers. Approaches to strengthening EDAT focus on introducing evidence-based guidelines, job aids and diagnostic tools; supporting capacity building of health care personnel, private providers and community-based workers and improving supply chain management through regular stock monitoring and RDT and ACT distribution.

A delay between onset of fever and treatment prolongs human suffering and allows further transmission from human to mosquito. Reducing the delay requires malaria services close to the communities, particularly in remote areas where travel to a health center is challenging. Early (and accurate) diagnosis is made possible through rapid diagnostic tests (RDTs). Use of RDTs also ensures that only patients parasitologically diagnosed with malaria get the treatment along with counseling on treatment adherence, limiting the emergence and spread of drug-resistant malaria. Early treatment with artemisinin-based combination therapies (ACTs) and low-dose primaquine prevents further transmission.

HS-RDT Performance Analysis

Asymptomatic low-density malaria infections are contributing to ongoing malaria transmission especially in areas close to reaching elimination objectives. According to ongoing studies, the ability of individuals to carry low-density malaria infections and have minimal clinical symptoms is believed to be the consequence of exposure-related clinical immunity, resulting in the suppression of parasitemia, and has been observed in both high- and low-transmission settings (American Journal of Tropical Medicine and Hygiene). Standard rapid diagnostic tests (RDTs) are reported missing a proportion of sub-microscopic malaria infections (Malaria Journal). Highly sensitive RDTs (HS-RDT) offer the ability to detect parasite densities lower than that of standard RDTs. This could allow detection prior to symptom development and prevent further transmission. Combination HS-RDT could be more cost-effective and practical because programmes could detect a greater proportion of infections spending less time in the field tracking every case and launching easier-to-implement screening and treatment campaigns (Malaria Journal).

Igniting popularity among the topic of HS-RDTs’ is the Alere™ Malaria Ag Pf ultra-sensitive RDT which was released in April 2017. Using the same immunochromatographic cassette platform and volume requirements, the HS-RDT displays about a ten-fold lower limit of detection (LOD~80 pg/mL) than current best-in-class RDTs. (PLOS Journal). Studies on the performance of this device revealed a more accurate and quicker diagnosis.

  • Study 1: Performance of HS-RDT for detecting malaria in peripheral and placental blood samples from pregnant women in Colombia. Results showed improved sensitivity of the HS-RDT over LM and conventional RDTs for detecting gestational and placental malaria, particularly in asymptomatic women, indicating the potential value of this test for managing malaria in pregnancy. (PLOS Journal)

Table 1: Accuracy of LM, PF/PV RDT, and HS-RDT for the diagnosis of P. falciparum infections in peripheral blood of pregnant women

Interpretation: the results of different diagnostic tools in this study look comparable by agreement level with slight higher sensitivity of HS-RDT than other tests.

Table 2: Performance of LM, Pf/PV RDT, and HS-RDT for detecting P. falciparum in peripheral blood of symptomatic and asymptomatic pregnant women

Interpretation: the results of the study are quite comparable by validity and predictive value for symptomatic patients. However, HS-RDT revealed the highest sensitivity for asymptomatic pregnant women.

  • Study 2: Performance of High-Sensitivity Rapid Diagnostic Test for falciparum Malaria in Asymptomatic Individuals from Uganda and Myanmar and Naïve Human Challenge Infections. Results showed the HS-RDT showed a greater than 10-fold limit of detection for HRP2 compared with the RDT. (American Journal of Tropical Medicine and Hygiene).

Table 3: showing positivity by the Q-plex HRP2 assay, uRDT, and the RDT for IBSM specimens with parasite density detectable by qRT-PCR

Interpretation: the significant different between uRDT from cRDT was observable only after five days post induced blood stage malaria (IBSM) challenge.

Table 4: showing performance of the RDT vs the HS-RDT (uRDT) 

The sample sizes for this study: IBSM: 93, Myanmar 493, Uganda: 607 in Das et al 2017, AJTMH. The better performance by uRDT over cRDT in asymptomatic patients from Myanmar and Uganda as well as 9 participants in the IBSM study is highly indicative of the utility of uRDT as a tool for malaria elimination.

As mentioned by the WHO, parasitological confirmation is necessary for a suspected malaria case to be confirmed. Early diagnosis and treatment (EDAT) among asymptomatic individual will accelerate the move towards malaria elimination. Drug resistant malaria occurs mostly among Plasmodium falciparum cases especially in the GMS countries. EDAT for Plasmodium falciparum infection could contribute to the reduction of artemisinin resistant malaria (ARM). Development of highly sensitive rapid diagnostic tests is still in early stages. However, as nations move closer to achieving malaria elimination goals, the need for more sensitive rapid diagnostic tests (uRDTs) for detecting malaria parasites at low parasitemia will increase.

Relevant resources on HS-RDT: