Fig 1.
Cumulative DALYs lost of afflicted populations due to the NTDs human African trypanosomiasis, chagas disease, schistosomiasis, leishmaniasis, lymphatic filariasis, onchocerciasis, taeniasis cysticercosis, echinococcosis, dengue, trachoma, rabies, leprosy, and soil-transmitted helminthiases. World map adapted from WHO [8]. DALY, disability-adjusted life year; NTD, neglected tropical disease; WHO, World Health Organization.
Fig 2.
Three types of PoC diagnostic tests.
A biological sample (such as blood, urine, saliva, sweat, etc.) can be utilized for various types of PoC diagnosis. Left: immunological PoC test. A biological sample is dropped unto the sample pad of a lateral flow assay, which acts as a filtering unit to sieve out unnecessary constituents. Upon administration of a reaction buffer (or its automated release), the analyte flows through the reagent pad, wherein an antigen–antibody complex is formed. Driven by capillary action, this complex migrates to the next zone with control and test lines. While the appearance of a visible color at the test line confirms the infection, the control line signal ensures the test functionality. Middle: nucleic acid–based PoC test. Here, genetic material of a pathogen serves as the analyte. DNA/RNA from the pathogen is extracted from infected host cells or circulating cell free within the clinical sample (body fluids). While extracted RNA is first reverse transcribed to obtain cDNA, extracted DNA can be directly amplified using PCR or using isothermal amplification (e.g., RPA or LAMP), typically in a fully automated portable unit. In some systems, the amplified DNA is then used for CRISPR/Cas recognition or other downstream processing to yield a diagnostic result within a lateral flow assay or a microfluidic lab-on-a-chip device. NGS can also be utilized to identify specific diseases using a portable sequencer. Right: biomarker-based PoC test (other than antigen biomarkers). A biological sample is administered onto the test pad that in this case has specific surface-bound molecules such as aptamers that target the analyte. Upon successful interactions, a visible color readout is obtained. The test can be in the form of separate wells. LAMP, loop-mediated isothermal amplification; NGS, next-generation sequencing; PCR, polymerase chain reaction; PoC, point-of-care; RPA, recombinase polymerase amplification.
Table 1.
NTD-specific status quo of existing PoC test and future implementation needs for PoC tests.
Fig 3.
Venn diagram depicting the PoC implementation needs for various NTDs.
After reviewing the 24 NTDs (see Supporting information and Table 1), NTDs were placed in the colored circles based on their PoC implementation need. The legends indicate the particular diagnostic need of the NTD. NTDs in bold depict priority for PoC diagnoses as set in WHO’s 2021–2030 roadmap [8]. NTD, neglected tropical disease; PoC, point-of-care; WHO, World Health Organization.
Fig 4.
Diagnostic insufficiencies for NTDs.
NTDs were ranked in the order of diagnostic insufficiencies (black bars) as deduced from 3 parameters: diagnostics technology (purple), availability (blue), and awareness (red), and scored for “action critically needed” to “in control.” Information was obtained from a literature survey, including comprehensive recent reports from WHO, particularly WHO 2021–2030 roadmap [8] and the diagnostic technical advisory group for NTDs report [20]. Data were critically analyzed to gather diagnostic insufficiencies for individual diseases. NTD, neglected tropical disease; WHO, World Health Organization.
Fig 5.
The healthcare paradox for NTDs in endemic regions.
At the lowest level, the healthcare system in the NTD endemic region has minimally trained CHWs capable of providing referrals to a level up such as local dispensaries with limited resources including technicians and/or midwives, followed by health centers with trained medical professionals, laboratory space, equipment, and/or inpatient wards. These CHWs at the base of the pyramid also play a vital role in facilitating mobile health outreach services, thereby bridging the gap between patients and medical facilities. One level further up is adequately equipped provisional hospitals followed by fully functional national hospitals at the top of the pyramid. Notably, the burden of NTDs is highest at the lowest healthcare level. This indicates the healthcare paradox, i.e., the highest NTD needs occur at the base of the pyramid where resources are inadequate, and, thus, the disease spreads further due to unmet healthcare needs. To interrupt this vicious cycle of disease endemicity, easy-to-use NTD diagnostics should be introduced to the CHWs at the lowest level. Bringing NTD diagnostics at the doorstep of the endemic populations will ensure efficient disease diagnosis and treatment, reduce costs, and thereby alleviate the healthcare burden. CHW, community healthcare worker; NTD, neglected tropical disease.