Long-term sequelae of chikungunya virus disease: A systematic review.

SARS-CoV-2 is not unique in its ability to cause post-acute sequelae; certain acute infections have long been associated with an unexplained chronic disability in a minority of patients. These post-acute infection syndromes (PAISs) represent a substantial healthcare burden, but there is a lack of understanding of the underlying mechanisms, representing a significant blind spot in the field of medicine. The relatively similar symptom profiles of individual PAISs, irrespective of the infectious agent, as well as the overlap of clinical features with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), suggest the potential involvement of a common etiopathogenesis. In this Review, we summarize what is known about unexplained PAISs, provide context for post-acute sequelae of SARS-CoV-2 infection (PASC), and delineate the need for basic biomedical research into the underlying mechanisms behind this group of enigmatic chronic illnesses. Certain acute infections (including SARS-CoV-2) are associated with an unexplained chronic disability in a minority of patients; this Review summarizes what is known about these understudied and complex illnesses. 

/pdf/unexplained-post-acute-infection-syndromes-1bysqesx.pdf

Unexplained post-acute infection syndromes

Background Chikungunya is a mosquito-borne disease caused by an arthritogenic alphavirus, with four genotypes: East Central South African (ECSA), West African, ECSA-diverged or Indian Ocean Lineage (IOL) and Asian lineage. Overall, the disease is self-limited; however, in some patients, joint pain and other non-specific symptoms can last for months or years. This systematic review and meta-analysis aims to estimate the proportion of people that self-report chikungunya-related chronic non-specific symptoms. Methods Medline, EMBASE, Global Health Library and Scopus were searched for articles published before March 2017. Case-control, cohort, cross-sectional, clinical trials studies and outcome-independent case series were eligible. It was estimated that the proportion of patients who did not recover, by virus genotype, and by the time between disease onset and assessment of chronic symptoms. Results A total of 38 studies were included in the review and 34 in the meta-analysis. Of 6532 chikungunya patients, 3157 did not recover fully after 3 months. The overall no recovery rate associated with chikungunya was 43% (95% CI, 35-52%); Inter-genotype group heterogeneity was observed, the highest prevalence in the ECSA-diverged genotype: 50% (95% CI; 40-60%), followed by the Asian lineage genotype: 36% (95% CI; 20-52%). After 12 months follow-up, the overall no-recovery rate was 21% (95% CI; 19-22%). Conclusion The evidence suggests that the prevalence of chronic discomfort associated with chikungunya illness varies by virus lineage. The proportion of people that do not fully recovered after chikungunya was high and, therefore, health authorities must prepare to treat patients with symptoms of long-lasting chikungunya adequately addressing the physical, psychological and social needs.

Chikungunya chronic disease: a systematic review and meta-analysis.

Summary


Background: Prospective community data on arthropathy following Chikungunya (CHIKV), a self-limiting, arboviral infection, causing debilitating arthropathy are lacking. The clinical profile of chronic rheumatic-musculoskeletal (RMSK) pain and disorders, captured inadvertently about 15 months following a CHIKV epidemic is described.



Materials and Methods:  Patients with RMSK pain following the CHIKV epidemic in 2007 were identified from a randomly selected population of 5277 (Age > 15 years) in a village in south India, using a validated questionnaire-based house-to-house survey. Typical narration, records and serology were relied upon to classify CHIKV. Respondents who recorded active pain sites on a human mannequin were evaluated by Rheumatology physicians.



Results:  A total of 1396 CHIKV infected individuals with painful MSKD were identified, of whom 437 patients (mean age: 48.37 ± 13.62 years; 71.6% women) who were naive to RMSK pain prior to the epidemic were studied in detail. Incidence of RMSK pain and disorders in the naive group was 8.3% (437/5277). Knee was the commonest self-reported pain site (83.3%). Majority of the patients (57%) had postviral non-specific polyarthralgia. Soft tissue rheumatism was very common (27.7%). Rheumatoid arthritis and seronegative spondyloarthritis were observed in 6 and 11 patients, respectively.



Conclusions:  Although a causal association could not be established, this study has unravelled a wide spectrum of unrecognised post-CHIKV chronic RMSK disorders. Aetiopathogenesis and risk factors of chronicity need to be studied further.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1742-1241.2011.02792.x

Rheumatic-musculoskeletal pain and disorders in a naïve group of individuals 15 months following a Chikungunya viral epidemic in south India: a population based observational study.

RATIONALE FOR REVIEW Young adults of childbearing age and pregnant women are travelling more frequently to tropical areas, exposing them to specific arboviral infections such as dengue, zika and chikungunya viruses, which may impact ongoing and future pregnancies. In this narrative review, we analyse their potential consequences on pregnancy outcomes and discuss current travel recommendations. MAIN FINDINGS Dengue virus may be associated with severe maternal complications, particularly post-partum haemorrhage. Its association with adverse fetal outcomes remains unclear, but prematurity, growth retardation and stillbirths may occur, particularly in cases of severe maternal infection. Zika virus is a teratogenic infectious agent associated with severe brain lesions, with similar risks to other well-known TORCH pathogens. Implications of chikungunya virus in pregnancy are mostly related to intrapartum transmission that may be associated with severe neonatal infections and long-term morbidity. TRAVEL RECOMMENDATIONS Few agencies provide specific travel recommendations for travelling pregnant patients or couples trying to conceive and discrepancies exist, particularly regarding Zika virus prevention. The risks significantly depend on epidemiological factors that may be difficult to predict. Prevention relies principally on mosquito control measures. Couples trying to conceive and pregnant women should receive adequate information about the potential risks. It seems reasonable to advise pregnant women to avoid unnecessary travel to Aedes spp. endemic regions. The current rationale to avoid travel and delay conception is debatable in the absence of any epidemic. Post-travel laboratory testing should be reserved for symptomatic patients.

https://serval.unil.ch/resource/serval:BIB_A8691B46321F.P001/REF.pdf

Dengue, Zika and chikungunya during pregnancy: pre- and post-travel advice and clinical management.

Objective. We investigated the effects of chronic rheumatic and musculoskeletal symptoms on the functional status of people affected by the chikungunya (CKG) epidemic in the Calicut District, Kerala, South India in 2009. Methods. A cross-sectional house-to-house survey was conducted 18 months after the CKG epidemic to assess functional status of individuals with post-epidemic persistent pain. All respondents over age 15 years with persistent pain fitting the epidemiological case definition were included. Participants’ functional status was assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI). Factors affecting severity of HAQ-DI were analyzed by ordinal regression. Results. Of 3869 subjects interviewed, 1195 (34.3%) had a positive history of CHIKV virus infection (epidemiological or confirmed); 36.28% (624/1720) of CKG-affected individuals had persistent pain 18 months post epidemic. Mean age of those affected was 48.22 ± 15.6 years; 23.2% had no disability, while 16.2% had moderate to severe disability on the HAQ-DI. Significant factors affecting severity of disability on HAQ-DI included previous rheumatic musculoskeletal disease (OR 2.27), joint and soft-tissue involvement (OR 3.74), only joint involvement (OR 2.14), female sex (OR 1.44), diet (OR 4.73), and history of joint swelling (OR 1.72). Conclusion. Persistence of pain noted in post-CKG disease resulted in significantly deteriorated functional status of those affected.

https://www.jrheum.org/content/jrheum/43/2/440.full.pdf

Disability with Persistent Pain Following an Epidemic of Chikungunya in Rural South India.

Pre-rheumatoid arthritis (pre-RA) is the preclinical period of the disease that precedes the onset of clinically apparent RA. It includes the interaction between genetic and environmental risk factors and development of disease-related autoantibodies and joint symptoms and signs, which may be considered nonspecific or unclassified for RA. A better understanding of the pre-RA stage will be useful in developing screening programs for early detection of RA. Identifying and modifying risk factors such as smoking, periodontitis, obesity, viral infections, and hormonal or dietary factors will be useful in preventing RA in susceptible population.

Pre-rheumatoid arthritis and its prevention.

Chikungunya (CHIK) is an arboviral infection caused by the chikungunya virus. An unusual feature of CHIK is its long periods of quiescence followed by an epidemic of devastating severity that can involve millions of people. Manifestations of CHIK range from a mild self-limiting febrile illness with arthralgia and rash to crippling acute and lingering debilitating arthritis. In about 10–60% of patients, musculoskeletal symptoms may persist for up to 3–5 years. Management is mainly symptomatic, with analgesics, antipyretics and non-steroidal anti-inflammatory agents. Ecological changes together with alterations in the viral genome facilitate the development of newer variants with greater pathogenicity, a matter of great concern. The social and economic burdens to a society as a result of CHIK epidemics have generated a considerable interest in the scientific community to decipher the reasons underlying myriad manifestations and to develop management strategies for tackling the menace of CHIK across the globe.

/pdf/chikungunya-infection-a-re-emerging-epidemic-2nczpcrdhv.pdf

Chikungunya Infection: A Re-emerging Epidemic

Clinical profile and long-term sequelae of Chikungunya fever

OBJECTIVE Rheumatoid arthritis (RA) is a multifactorial disease; it leads to disabling and painful chronic inflammatory arthritis. Its onset may be delayed or even prevented by modifying the risk factors involved. Many genetic, epigenetic, and environmental factors are implicated in the pathogenesis of RA. The objectives of this case-control study were to assess various risk factors in our population and to compare the same with age- and sex-matched controls. METHODS We studied 118 cases with RA diagnosed using the EULAR criteria. In total, 581 age- and sex-matched controls were selected. Each individual was administered a separate questionnaire regarding their risk factors (known risk factors were studied). The implicated dietary factors were incorporated in a food frequency questionnaire (FFQ) and administered to both cases and controls. Comparison was made between those who consume an item at a particular frequency, who consume less, and who consume nothing at all. Among those who consume, each group was re-compared. Statistical analysis was conducted using Statistical Package for Social Sciences (IBM Corp.; Armonk, NY, USA). RESULTS There was significant relationship for family history, periodontitis, history of chikungunya, and sun exposure (p<0.05). Association with various food items was studied using the FFQ, but the relationship was inconsistent, probably due to consumption of modified diet by the persons with RA. Also, a majority of cases were females and nonsmokers for assessing an association with smoking habits. CONCLUSION In our population, previous infections (e.g., chikungunya and poor oral hygiene with periodontitis) were the prominently observed risk factors. Also, smoking was less common among women, and probably contributed less, as majority of cases were females. For dietary pattern association, a prospective cohort study may be needed.

Binoy J Paul

Papers

Disability with Persistent Pain Following an Epidemic of Chikungunya in Rural South India.

Pre-rheumatoid arthritis and its prevention.

Chikungunya Infection: A Re-emerging Epidemic

Clinical profile and long-term sequelae of Chikungunya fever

Risk factor assessment of rheumatoid arthritis in North Kerala.