The significance of molecular diagnostics in low-resource environments for infectious diseases

The best practice for expanding laboratory capacity in environments with limited resources is to choose methods that are feasible and long-lasting. For many years, molecular diagnostics were seen as “inappropriate” despite their usefulness and accuracy. This was because they were thought to be too precise, costly, prone to contamination, and technically complex to be employed in situations where infrastructure was outdated, skills were scarce, or resources were limited.

Traditional culture-based clinical microbiology, which is usually considered “appropriate,” has proven to be extremely challenging to maintain at the necessary standard in low-income environments without outside assistance. While some diseases are inexpensive to cultivate, others need a high expense. Long turnaround times and quality assurance problems further limit the influence of culture-based approaches on patient care, infection prevention and control, and outbreak responses.

Serological techniques, while usually considerably faster and easier, frequently lack specificity, are not available for many infections, and do not offer the breadth and depth of information required to make wise judgments. In addition, supply networks for pathogen-specific diagnostics are intricate, prone to disruption, and challenging to modify for novel infections.

In addition to having few resources, the majority of African nations also deal with a high prevalence and wide range of infectious diseases. Fever is the most frequent symptom that prompts a patient to visit a medical facility in Nigeria. It can be caused by over 200 different diseases, such as hemorrhagic viruses, malaria parasites, and Salmonella enterica. Without costly new gear, tissue culture, or biosafety upgrades, many of the potentially fatal infections cannot be reliably discovered by culture.

The necessity for effective molecular diagnostics is highlighted by the combination of a wide pathogen spectrum and resource limitations, which are also present in many high-infectious disease burden settings in South Asia and South America. The inclination towards “simple” culture-based techniques stems from a concentration on individual diseases and is frequently funded and driven by research; yet, it is not appropriate to address the needs of the larger health system. Molecular diagnostics are versatile enough to quickly adapt to emerging threats and, despite their high upfront cost, are cost-effective since they provide greater diagnostic precision for a wide range of pathogens while utilizing a small consumable palette.

Molecular equipment is typically kept for specialized or reference-only testing in environments with limited resources. However, more widespread use of these resources will result in economies of scale and enable the commercial viability of local testing material manufacturing in the low-income nations that most require it. However, given a tight budget, inadequate equipment, and a shortage of trained staff, is it really feasible to implement molecular diagnostics in this kind of environment? A workable proof of concept is offered by COVID-19. The number of public health laboratories in Nigeria that are capable of performing molecular identification of SARS-CoV-2 in clinical specimens climbed from four to 72 between January 2020 and January 2021. Pooled procurement, graded training, and excellent coordination and control enabled this expansion.

Parallel expansions were made in ancillary services like biosafety, supply chain management, bioengineering, and quality assurance. There have been reports of similar exponential growth in the capability for public health testing from other LMIC contexts. Promptly consolidating and expanding upon these successes is the optimal approach to return significant COVID-19 diagnostic expenditures to other infectious illnesses. Case studies of successful implementations of molecular diagnostics in low-income environments go much beyond COVID-19. Using molecular approaches, the unexpected development of Yellow fever and Ebola hemorrhagic viruses in Nigeria during the last ten years was quickly detected weeks before more conventional reference procedures could be implemented. In both cases, the public health response was led by early insights obtained from the advanced information obtained from on-the-spot PCR testing.

The uncommon etiologic agents of neonatal sepsis in hospitals in the Gambia could be concurrently identified, their antibiotic resistance profiles could be ascertained, and nosocomial outbreaks could be pinpointed thanks to culture followed by whole-genome sequencing (WGS). The analysis of archived samples from Bangladesh revealed that molecular approaches can boost pathogen identification in meningitis patients several times over. This quadrupled the conventional sensitivity and allowed for the retrospective discovery of an outbreak of the chikungunya virus.

These and numerous other instances make a compelling justification for the regular application of molecular diagnostics, even in the face of obstacles that are generally manageable. As previously said, “PCR is an easy thing to do badly,” and even the most forward diagnostic supporters fear the possibility of waste, contamination, or incorrect data interpretation from carelessly performed molecular testing. Certain PCR limitations may be lessened with WGS. Increasing access to external quality assurance and strengthening the molecular biology knowledge base in low-income nations are urgent priorities.

Miniaturization will reduce the need for pricey chemicals, while microfluidics may shield delicate processes from error. One example is the use of Gene Xpert for testing during the Ebola and SARS-CoV-2 outbreaks to detect tuberculosis in settings with limited resources.

Although millions of people who currently lack access to testing will finally be able to obtain it, molecular diagnostics will not and should not replace culture anytime soon. It has the ability to completely transform population surveillance in areas that are difficult to access and to cover a lot of terrain with little resources. For instance, identifying hotspots for transmission and focusing vaccination efforts can be aided by the detection of faeco-oral infections. Typhoid is a disease for which routine blood cultures are not very sensitive, and environmental source cultures are much less sensitive. However, DNA-based techniques for pathogen detection, which have been successfully applied to map typhoid hot spots and target polioviruses in the latter stages of eradication, are easy to use and efficient for detecting S. enterica and other infections. Similar techniques can be applied to SARS-CoV-2, enteric viruses, and cholera.

The potential that molecular diagnostics currently hold is just the tip of the iceberg, and the time has come to solve the obstacles preventing their wider application. Robust procurement, shipping and handling, stock management, and waste disposal procedures need to take the place of emergency solutions modeled after pandemics to address supply chain breakdowns that beset health systems and laboratories in low-income countries. Nowadays, a lot of labs have solar backup systems built to deal with regular power outages. During the next ten years, low-resource but rapidly expanding diagnostic landscapes will be populated by “smart” equipment that can resume operations without any problems following a power outage.

The next generation of truly relevant equipment, like Oxford nanopore sequencers, which are currently available for specific applications, will only need an intermittent power source. Outside of biomedicine, innovative answers to further supply chain and infrastructure shortages are also required. National public health institutions have demonstrated leadership in a number of settings and are best positioned to offer the governance, coordination, and support for the growth of public health diagnostics that is sorely required. Rather than circumventing the unwillingness to customize molecular diagnostics for the infrastructure-poor areas where they are most needed, we can and should innovate to suit them for purpose.

Source

Okeke, I. N., & Ihekweazu, C. (2021). The importance of molecular diagnostics for infectious diseases in low-resource settings. Nature reviews. Microbiology, 19(9), 547–548. https://doi.org/10.1038/s41579-021-00598-5

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