Global and Low-Resource Perspectives on ME/CFS
1 Arron et al. 2024 — ME/CFS as a Neglected Disease
Full Citation:: Arron HE, Marsh BD, Kell DB, Khan MA, Jaeger BR, Pretorius E. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: the biology of a neglected disease. Frontiers in Immunology. 2024;15:1386607. DOI:: 10.3389/fimmu.2024.1386607 PMID:: 38887284 PMCID:: PMC11180809 Study Design:: Narrative review Key Findings::
Characterises ME/CFS as a “neglected disease” with biological basis centred on microclots and amyloid fibrin
Co-author Pretorius is based in South Africa — one of few ME/CFS research contributions from the African continent
Argues that ME/CFS research is concentrated in high-income countries, creating a global evidence gap Conclusion:: ME/CFS meets criteria for a neglected disease in global health; biological mechanisms (microclots) provide testable targets. Limitations:: Narrative review; Pretorius group’s microclot hypothesis is controversial; no primary data. Certainty Assessment::
Quality: Medium (Frontiers in Immunology, narrative review)
Sample: N/A (review)
Replication: N/A
Score: 0.65 Study Date Era:: Post-IOM 2015–present
2 Condé et al. 2026 — Post-Dengue Fatigue Systematic Review and Meta-Analysis
Full Citation:: Condé A, Maillard O, Rodrigo C, Bertolotti A, Sandler CX, Lloyd AR, Gérardin P. Post-Infectious Fatigue and Depression Following Dengue: A Systematic Review and Meta-Analysis of Associated Factors. Reviews in Medical Virology. 2026;36(3):e70164. DOI:: 10.1002/rmv.70164 Study Design:: Systematic review and meta-analysis Key Findings::
First systematic review quantifying post-dengue fatigue
Dengue endemic in 100+ countries, predominantly LMICs
Post-infectious fatigue prevalence and associated factors systematically assessed
Establishes that arboviral infections in LMICs produce chronic fatigue syndromes comparable to post-EBV CFS Conclusion:: Post-dengue fatigue is a significant public health burden in dengue-endemic LMICs, largely unrecognized as a post-infectious fatigue syndrome. Limitations:: Heterogeneity in fatigue definitions across studies; limited number of eligible studies; no ME/CFS diagnostic criteria applied. Certainty Assessment::
Quality: Medium-High (Reviews in Medical Virology, systematic review with meta-analysis)
Sample: Systematic review of published studies
Replication: First systematic review of this question
Score: 0.75 Study Date Era:: Post-IOM 2015–present
3 Duvignaud et al. 2018 — Post-Chikungunya Chronic Fatigue (TELECHIK Cohort)
(Duvignaud2018chikungunyaFatigue?)
Full Citation:: Duvignaud A, Fianu A, Bertolotti A, et al. Rheumatism and chronic fatigue, the two facets of post-chikungunya disease: the TELECHIK cohort study on Reunion island. Epidemiology and Infection. 2018;146(5):633–641. DOI:: 10.1017/S0950268818000031 PMID:: 29486812 PMCID:: PMC5892425 Study Design:: Prospective cohort study Sample Size:: Reunion Island chikungunya outbreak survivors followed over 30 months Key Findings::
Two major post-chikungunya sequelae: chronic rheumatism and chronic fatigue
Chronic fatigue affected substantial proportion at long-term follow-up
Demonstrates post-arboviral fatigue as major public health burden in tropical settings Conclusion:: Post-chikungunya chronic fatigue mirrors post-infectious CFS — supports arboviral infections as ME/CFS triggers in tropical LMIC settings. Limitations:: Single outbreak setting; no ME/CFS diagnostic criteria applied; tropical island (Reunion is French overseas department, not typical LMIC). Certainty Assessment::
Quality: Medium (Epidemiology and Infection, prospective cohort)
Sample: Moderate cohort size
Replication: Single cohort at Reunion Island
Score: 0.70 Study Date Era:: CCC/ICC 2003–2015
4 Vester et al. 2026 — Burden of Disease Scoping Review
Full Citation:: Vester P, Boudouroglou-Walter S, Schreyögg J, Wieting C, Blome C. Burden of Disease in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Scoping Review. Applied Health Economics and Health Policy. 2026;24(1):147–161. DOI:: 10.1007/s40258-025-01006-2 PMID:: 40986167 PMCID:: PMC12790524 Study Design:: Scoping review Key Findings::
Consistent severe QoL impairment in ME/CFS (EQ-5D scores ~0.40–0.55, lower than MS/stroke)
Economic burden estimated at $18–51B in the US
No non-high-income-country burden estimates identified in the review
Gap: burden of disease data entirely absent from LMICs Conclusion:: ME/CFS imposes severe disease burden comparable to major chronic diseases; global data gap on LMIC burden is a critical evidence void. Limitations:: Scoping review, not systematic; heterogeneity in burden measures; high-income country data only. Certainty Assessment::
Quality: Medium (Applied Health Economics and Health Policy, systematic search)
Sample: Scoping review of published studies
Replication: First scoping review of ME/CFS disease burden
Score: 0.60 Study Date Era:: Post-IOM 2015–present
5 Sarker et al. 2024 — Bangladesh ME/CFS RCT Protocol
(Sarker2024bangladeshRCTprotocol?)
Full Citation:: Sarker AH, Hossain KMA, Kabir MF, et al. Comparing effectiveness of physiotherapy versus drug management on fatigue, physical functioning, and episodic disability for myalgic encephalomyelitis in post-COVID-19 condition: a study protocol of randomized control trial. Trials. 2024;25(1):321. DOI:: 10.1186/s13063-024-08077-x PMID:: 38750586 PMCID:: PMC11094988 Study Design:: Published RCT protocol Sample Size:: Planned RCT from Bangladesh Key Findings::
First registered ME/CFS clinical trial from Bangladesh
Testing physiotherapy vs drug management in post-COVID ME
Uses episodic disability framework relevant to LMIC settings where continuous disability assessments are impractical
Represents emerging ME/CFS research capacity in South Asia Conclusion:: LMIC ME/CFS research is emerging, led by post-COVID clinical needs in Bangladesh. Limitations:: Protocol only — no efficacy data; Fukuda criteria applied; physiotherapy approach may be contraindicated in PEM+ patients. Certainty Assessment::
Quality: Medium (Trials journal, pre-registered RCT)
Sample: Planned, not yet reported
Replication: N/A (protocol)
Score: 0.50 Study Date Era:: Post-IOM 2015–present
6 Starcevic 1999 — Neurasthenia and Chronic Fatigue Syndrome
Full Citation:: Starcevic V. Neurasthenia: cross-cultural and conceptual issues in relation to chronic fatigue syndrome. General Hospital Psychiatry. 1999;21(4):249–255. DOI:: 10.1016/S0163-8343(99)00012-2 PMID:: 10514948 Study Design:: Comparative review Key Findings::
Maps conceptual relationship between neurasthenia (ICD-10) and CFS
Notes that neurasthenia remains prevalent diagnosis in China, East Asia, and parts of Eastern Europe
Global diagnostic expansion eliminates neurasthenia as label in some settings while CFS/ME emerge as functional replacement
Cultural framing determines whether fatigue is reported as psychological or somatic Conclusion:: CFS and neurasthenia are overlapping but culturally-moderated constructs; diagnostic labelling is shaped by local medical culture, not biology alone. Limitations:: 1999-era conceptual review; limited empirical data; pre-IOM diagnostic era. Certainty Assessment::
Quality: Medium (General Hospital Psychiatry, narrative review)
Sample: N/A
Replication: Cross-cultural comparisons consistent with Lee, Ware/Kleinman
Score: 0.50 Study Date Era:: Fukuda 1994–2003
7 Ware and Kleinman 1992 — Culture and Somatic Experience
Full Citation:: Ware NC, Kleinman A. Culture and somatic experience: the social course of illness in neurasthenia and chronic fatigue syndrome. Psychosomatic Medicine. 1992;54(5):546–560. DOI:: 10.1097/00006842-199209000-00003 PMID:: 1438658 Study Design:: Comparative anthropological analysis (China vs US) Key Findings::
Landmark cross-cultural comparison of neurasthenia in China and CFS in the United States
Different cultural idioms for similar fatigue syndromes — somatic idioms dominant in China, psychological in US
Social course of illness shaped by cultural norms about illness behaviour and legitimacy
Demonstrates that “the same” illness can present differently depending on cultural context Conclusion:: ME/CFS symptom expression is culturally moderated — global prevalence estimates using Western diagnostic criteria may misclassify cases in non-Western settings. Limitations:: Pre-Fukuda era; small qualitative samples; China vs US only (does not cover Africa, South Asia, Latin America). Certainty Assessment::
Quality: High (Psychosomatic Medicine, Arthur Kleinman — leading medical anthropologist)
Sample: Qualitative, small
Replication: Consistent with Lee 1995, 1998, 2000
Score: 0.55 Study Date Era:: Pre-1994
8 Lee 1998 — Neurasthenia in Contemporary Chinese Society
Full Citation:: Lee S. Estranged bodies, simulated harmony, and misplaced cultures: neurasthenia in contemporary Chinese society. Psychosomatic Medicine. 1998;60(4):448–457. DOI:: 10.1097/00006842-199807000-00010 PMID:: 9710290 Study Design:: Ethnographic and clinical review Key Findings::
Shenjing shuairuo (neurasthenia) remains culturally acceptable idiom for fatigue/distress in Chinese society
ME/CFS would be filtered through this culturally shaped lens if assessed with Western instruments
Body-centred distress expression reflects social norms about legitimate illness, not lack of psychological insight
Western diagnostic expansion (CFS, depression, anxiety) has partially displaced neurasthenia in urban/professional Chinese populations Conclusion:: CFS-like conditions in China are labelled neurasthenia; direct application of Fukuda/CCC criteria would produce artefactually low prevalence. Limitations:: Single-culture focus (Chinese); 1998 data may not reflect contemporary urbanisation effects. Certainty Assessment::
Quality: Medium (Psychosomatic Medicine, clinical-anthropological review)
Sample: N/A
Replication: Consistent with Ware/Kleinman 1992, Lee 2000
Score: 0.50 Study Date Era:: Pre-Fukuda / early Fukuda 1994–2003
9 National Academies 2024 — Common Research Agenda for Infection-Associated Chronic Illnesses
(NationalAcademies2024researchAgenda?)
Full Citation:: National Academies of Sciences, Engineering, and Medicine. Toward a Common Research Agenda in Infection-Associated Chronic Illnesses: Proceedings of a Workshop. Washington, DC: National Academies Press; 2024. DOI:: 10.17226/27462 PMID:: 38648305 Study Design:: Workshop proceedings Key Findings::
Convened experts across ME/CFS, Long COVID, post-Lyme, and other infection-associated chronic illnesses (IACI)
Called for common research frameworks, shared biomarkers, and international standardization
Global health dimension present but underdeveloped — LMIC perspectives largely absent from workshop
Identified cross-disease mechanisms: immune dysregulation, autonomic dysfunction, neuroinflammation Conclusion:: First major institutional effort to unify post-infectious fatigue research; LMIC engagement a recognised gap. Limitations:: US-centric workshop; LMIC representation minimal; proceedings, not peer-reviewed research. Certainty Assessment::
Quality: High (National Academies institutional authority)
Sample: Workshop with expert panels
Replication: N/A
Score: 0.70 Study Date Era:: Post-IOM 2015–present
10 Podell et al. 2020 — Documenting Disability in ME/CFS
(Podell2020documentingDisability?)
Full Citation:: Podell R, Dimmock ME, Comerford BB. Documenting disability in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Work. 2020;66(2):339–352. DOI:: 10.3233/WOR-203178 PMID:: 32568153 Study Design:: Practical guidance / review Key Findings::
Practical framework for documenting ME/CFS functional impairment for disability claims
ME/CFS coded as G93.3 in ICD-10, 8E49 in ICD-11
Highlights disconnect between ICD coding existence and practical disability recognition
Relevant to LMIC settings where disability insurance systems are weak or absent — functional documentation can support claims in any system Conclusion:: Existence of ICD codes for ME/CFS does not guarantee disability recognition; documentation standards matter. Limitations:: US-centric legal/insurance framework; not specific to LMIC contexts. Certainty Assessment::
Quality: Medium (Work journal, expert guidance)
Sample: N/A
Replication: N/A
Score: 0.65 Study Date Era:: CCC/ICC 2003–2015
11 Simani et al. 2021 — Post-COVID CFS Prevalence in Iran
Full Citation:: Simani L, Ramezani M, Darazam IA, Sagharichi M, Aalipour MA, Ghorbani F, Pakdaman H. Prevalence and correlates of chronic fatigue syndrome and post-traumatic stress disorder after the outbreak of the COVID-19. Journal of Neurovirology. 2021;27(1):154–159. DOI:: 10.1007/s13365-021-00949-1 PMID:: 33528827 PMCID:: PMC7852482 Study Design:: Cross-sectional prevalence study Sample Size:: Hospitalised COVID-19 patients in Tehran, Iran Key Findings::
17.5% of hospitalised COVID-19 patients met Fukuda CFS criteria at 6-month follow-up
75% of CFS cases were female
First ME/CFS prevalence estimate from a middle-income Middle Eastern country
Post-infectious CFS in an LMIC mirrors patterns seen in high-income countries Conclusion:: Post-infectious ME/CFS prevalence in Iran is comparable to estimates from HICs; ME/CFS burden in middle-income settings is real but under-measured. Limitations:: Hospital-based sample (severe COVID); Fukuda criteria only; no baseline fatigue assessment; single centre; PTSD confounding. Certainty Assessment::
Quality: Medium (Journal of Neurovirology)
Sample: Moderate
Replication: Single centre in Iran
Score: 0.55 Study Date Era:: Post-IOM 2015–present
12 Miller et al. 2026 — Post-Acute Sequelae Across Epidemic History
Full Citation:: Miller CM, Moen JK, Iwasaki A. The lingering shadow of epidemics: post-acute sequelae across history. Trends in Immunology. 2026;47(1):9–18. DOI:: 10.1016/j.it.2025.10.010 PMID:: 41350176 Study Design:: Historical review Key Findings::
Post-acute sequelae documented after influenza 1918, polio, Ebola, SARS, and COVID-19
Chronic fatigue is a common thread across post-epidemic syndromes
Pandemics produce long-term disability disproportionately in settings with poor acute care infrastructure
Global health relevance: post-infectious fatigue burden follows infectious disease burden geographically Conclusion:: Post-infectious fatigue syndromes are historically recurrent; LMICs with high infectious disease burden likely carry disproportionate post-infectious fatigue burden. Limitations:: Historical review, not empirical; does not quantify LMIC burden. Certainty Assessment::
Quality: Medium (Trends in Immunology, Iwasaki lab)
Sample: N/A (historical review)
Replication: N/A
Score: 0.55 Study Date Era:: Post-IOM 2015–present
13 Wang et al. 2014 — Traditional Chinese Medicine for CFS (Systematic Review)
Full Citation:: Wang YY, Li XX, Liu JP, Luo H, Ma LX, Alraek T. Traditional Chinese medicine for chronic fatigue syndrome: a systematic review of randomized clinical trials. Complementary Therapies in Medicine. 2014;22(4):826–833. DOI:: 10.1016/j.ctim.2014.06.004 PMID:: 25146086 Study Design:: Systematic review of RCTs Sample Size:: 23 RCTs included (n=1,776 total) Key Findings::
TCM herbal formulations show signal for fatigue reduction compared to placebo or conventional treatment
Methodological quality of included trials generally low (high risk of bias, small samples)
Limited evidence precludes firm conclusions about specific TCM formulations
TCM widely available in East Asian healthcare systems — even modest efficacy has population-level relevance Conclusion:: TCM may benefit CFS patients but evidence quality is insufficient for guideline recommendations. Limitations:: High risk of bias in primary studies; heterogeneous interventions; small samples; 2014 search date (dated). Certainty Assessment::
Quality: Medium (Complementary Therapies in Medicine, Cochrane-style SR)
Sample: 23 RCTs, n=1,776
Replication: Consistent with subsequent TCM SRs
Score: 0.60 Study Date Era:: CCC/ICC 2003–2015
14 Kong et al. 2023 — TCM Mind-Body Exercises for CFS (Meta-Analysis)
Full Citation:: Kong L, Ren J, Fang S, et al. Effects of traditional Chinese mind-body exercises for patients with chronic fatigue syndrome: A systematic review and meta-analysis. Journal of Global Health. 2023;13:04157. DOI:: 10.7189/jogh.13.04157 PMID:: 37994837 PMCID:: PMC10666566 Study Design:: Systematic review and meta-analysis Key Findings::
Tai Chi, Qigong, Baduanjin evaluated across multiple RCTs
Moderate effect size on fatigue reduction
Mind-body exercises accessible in LMIC settings where pharmacological options are limited
No serious adverse events reported Conclusion:: TCM mind-body exercises are safe and moderately effective for CFS fatigue; relevant to LMICs where these practices are culturally embedded and low-cost. Limitations:: Moderate heterogeneity; most studies from China (generalizability to non-Chinese populations uncertain); unblinded (inherent to exercise interventions). Certainty Assessment::
Quality: Medium (Journal of Global Health)
Sample: Multiple RCTs pooled
Replication: Consistent with prior TCM exercise reviews
Score: 0.65 Study Date Era:: Post-IOM 2015–present
15 Wang et al. 2017 — Acupuncture and Moxibustion for CFS (Network Meta-Analysis)
Full Citation:: Wang T, Xu C, Pan K, Xiong H. Acupuncture and moxibustion for chronic fatigue syndrome in traditional Chinese medicine: a systematic review and meta-analysis. BMC Complementary and Alternative Medicine. 2017;17(1):163. DOI:: 10.1186/s12906-017-1647-x PMID:: 28335756 PMCID:: PMC5363012 Study Design:: Systematic review and network meta-analysis Sample Size:: 31 RCTs Key Findings::
Acupuncture and moxibustion show small-to-moderate effect on CFS fatigue
Acupuncture widely available in East Asian settings and increasingly in Indian traditional medicine contexts
Moxibustion (heat application at acupoints) also showed benefit
Network meta-analysis allowed indirect comparisons between modalities Conclusion:: Acupuncture is a moderately effective, low-risk option for CFS in settings where it is available and culturally accepted. Limitations:: Sham acupuncture controls difficult to blind; most studies from China; heterogeneity in acupuncture protocols. Certainty Assessment::
Quality: Medium (BMC CAM, now BMC Complementary Medicine and Therapies)
Sample: 31 RCTs
Replication: Consistent across TCM modality reviews
Score: 0.60 Study Date Era:: CCC/ICC 2003–2015