Covid-19 continues to cause huge disruption worldwide. As well as the ongoing immediate health impacts of the pandemic, and the delays and disruption to other healthcare services—the economic toll is also being felt across the world. The impact is particularly being felt in low and middle income countries (LMICs) like Nepal. [1] 

The disruption of health services is wide ranging. One of the areas that has been hardest hit is maternal and neonatal health services. Data collected between 1 January and 30 May 2020 from nine hospitals across the seven provinces in Nepal revealed that childbirth in hospital decreased by ~50% with an increase in hospital stillbirths and neonatal mortality. This period covered 12·5 weeks before the national lockdown and 9·5 weeks during the lockdown. [2] Other health services in South Asia have also been affected. Over a hundred dog bite victims per day used to come to the Sukraraj Tropical Medicine Hospital in Teku, Kathmandu to obtain the free anti-rabies vaccine. This is a given in Nepal after a dog bite as rabies is endemic in Nepal and the surrounding region, and is a fatal illness. Now only ~25 people per day are presenting, likely through the combination of lack of transport and fear of visiting hospitals because of the possibility of contracting covid-19.

Antimicrobial resistance (AMR), already a burgeoning problem in South Asia, is potentially set to get worse due to the pandemic. Findings from a survey administered across 82 hospitals in 23 countries suggest that broad-spectrum antibiotic use is common among covid-19 patients. [3] The most commonly prescribed antibiotic in the intensive care unit was piperacillin/tazobactam and prescribing was often based on clinical presentation rather than laboratory markers. There was substantial combined use of β-lactams and macrolides (or fluoroquinolones) reported. Although this report was predominantly from North America and Europe, anecdotally similar antibiotic prescription patterns are observed in Nepal and other South Asian hospitals where fluoroquinolone resistance is already high. [4] A plan for implementing antimicrobial stewardship guidelines for covid-19 needs to be devised and put into action, to prevent widespread, often unnecessary use of antibiotics in South Asia. 

Covid-19 has shifted research priorities and stalled other essential ongoing research. Almost all non covid-19 medical research in Nepal has come to a standstill and some projects that are due to start have been postponed. For example, all fever studies (randomised controlled trials (RCT) in diagnosis and treatment of tuberculosis, typhoid fever and other undifferentiated febrile illness) have discontinued or been postponed. Covid-19 is the priority for hospitals. To carry out any of these studies, a test needs to be instituted to rule out Sars-Cov-2 infection. Unfortunately, covid-19 PCR tests are expensive and cumbersome and require advanced laboratory facilities that are only available in few centres. Much-needed rapid antibody or antigen tests are currently unavailable or less reliable. In addition, recruitment into trials is more difficult because of reduced mobility due to lockdown and other interventions, and the general fear of contracting covid-19. These factors have severely negatively impacted research studies. 

Despite many problems generated by covid-19, the disease has afforded a unique opportunity for a better understanding of health research and methodologies in infectious diseases, which plague LMICs. 

The pandemic has highlighted the importance of large sample sizes for obtaining a reliable conclusion, the usefulness of randomised controlled trials vs observational studies, the role of robust and inexpensive rapid diagnostic tests (RDTs), and the importance of conducting well-designed vaccine studies and using those vaccines. Inadequate study sample sizes, unreliable RDTs, inadequate designs of RCTs, and underutilization of vaccines underpin (separately or together) many studies (on which recommendations are based) in tropical illnesses, including typhoid fever, leptospirosis, rickettsial, arboviruses, and spirochetal illnesses. [5-7] In an indirect way, covid-19 may help focus attention on better prevention, diagnosis, and treatment of these illnesses.   

While covid-19 has become the top public health and health research priority, it is essential now, especially in LMICs like Nepal, for decision-makers, funders, and researchers to start planning for a more comprehensive approach to research and clinical management of covid-19 that considers the context in which it occurs in relation to other infectious diseases and the presenting signs and symptoms. In planning for an integrated clinical management of acute febrile illnesses, a reliable, quality assured Sars-Cov-2 rapid diagnostic test will be an essential tool to providing a correct diagnosis. We strongly support the current call to action for a concerted global effort to fast track this. [8]

Fever—with or without respiratory or intestinal symptoms—is the common denominator to a range of common conditions in LMICs, some of which need to be treated with antibiotics. We need to be able to diagnose infectious diseases correctly to start effective, tailored treatments, and to avoid unnecessary treatments, like the use of “just in-case” antibiotics, which at best are ineffective, and at worst increase antimicrobial resistance. 

During this pandemic, it is incumbent upon us, local and international researchers, to draw attention not only to disruptions, but also to opportunities, and to shift to a positive narrative to mobilise for change.

Buddha Basnyat is director, Oxford University Clinical Research Unit-Nepal.

Olawale Salami is clinical trials project manager, Foundation for New Innovative Diagnosis (FIND), Geneva, Switzerland.

Abhilasha Karkey is vice director of Oxford University Clinical Research Unit-Nepal.

Catrin Moore is research group leader, Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.

Abhishek Giri is medical co-ordinator, Oxford University Clinical Research Unit Nepal, Patan Academy of Health Sciences, Kathmandu, Nepal.

Piero Olliaro is professor of Poverty-related Infectious Diseases at the University of Oxford, Oxford, UK and Head of Programme at FIND, Geneva, Switzerland

Competing interests: None declared. 

References:

1. https://blogs.worldbank.org/voices/covid-19-will-hit-poor-hardest-heres-what-we-can-do-about-it].
2. Kc A, Gurung R, Kinney MV, et al. Effect of the COVID-19 pandemic response on intrapartum care, stillbirth, and neonatal mortality outcomes in Nepal: a prospective observational study. The Lancet Global health 2020.
3. Beović B, Doušak M, Ferreira-Coimbra J, et al. Antibiotic use in patients with COVID-19: a ‘snapshot’ Infectious Diseases International Research Initiative (ID-IRI) survey. Journal of Antimicrobial Chemotherapy 2020.
4. Browne AJ, Kashef Hamadani BH, Kumaran EAP, et al. Drug-resistant enteric fever worldwide, 1990 to 2018: a systematic review and meta-analysis. BMC Med 2020; 18(1): 1.
5. Bhargava A, Ralph R, Chatterjee B, Bottieau E. Assessment and initial management of acute undifferentiated fever in tropical and subtropical regions. BMJ (Clinical research ed) 2018; 363: k4766.
6. Hepatitis E vaccine: why wait? Lancet (London, England) 2010; 376(9744): 845.
7. Basnyat B. Typhoid versus typhus fever in post-earthquake Nepal. The Lancet Global health 2016; 4(8): e516-7.
8.     Call to action: global crisis on testing – FIND, https://www.finddx.org/covid-19/call-to-action-testing/ Accessed: 2020-08-24