Chikungunya Outbreak in Country with Multiple Vectorborne Diseases, Djibouti, 2019-2020.

During 2019-2020, a chikungunya outbreak occurred in Djibouti City, Djibouti, while dengue virus and malaria parasites were cocirculating. We used blotting paper to detect arbovirus emergence and confirm that it is a robust method for detecting and monitoring arbovirus outbreaks remotely.

The challenging management of Rift Valley Fever in humans: literature review of the clinical disease and algorithm proposal.

Rift Valley Fever (RVF) is an emerging zoonotic arbovirus with a complex cycle of transmission that makes difficult the prediction of its expansion. Recent outbreaks outside Africa have led to rediscover the human disease but it remains poorly known. The wide spectrum of acute and delayed manifestations with potential unfavorable outcome much complicate the management of suspected cases and prediction of morbidity and mortality during an outbreak. We reviewed literature data on bio-clinical characteristics and treatments of RVF human illness. We identified gaps in the field and provided a practical algorithm to assist clinicians in the cases assessment, determination of setting of care and prolonged follow-up.

Clinical Features of Mycobacterium canettii Infection: A Retrospective Study of 20 Cases Among French Soldiers and Relatives.

BACKGROUND: Mycobacterium canettii forms part of the Mycobacterium tuberculosis complex. Mycobacterium canettii infections are mainly described in the Horn of Africa. The permanent presence of French soldiers in Djibouti raises the question of the risk of being infected with M. canettii. Here, we describe M. canettii infections among French military and their families between 1998 and 2015. METHODS: This retrospective study relied on 3 sources of data: the reference center for mycobacteria in the Biology Department at Percy Military Hospital in Paris, the French Military Center for Epidemiology and Public Health, and the scientific literature. After an exhaustive census of the strains, we studied the epidemiological data on 20 cases among French soldiers and their families. RESULTS: Twenty cases of M. canettii infections are reported, including 5 unpublished cases. Adenitis predominates (n = 15), especially in the cervico facial area and among children; 1 case was observed 1 month after dental care in Djibouti. The pulmonary forms were less frequent (n = 6), and 3 atypical forms are described. All patients had stayed in Djibouti. CONCLUSIONS: Cases of M. canettii infection among the French military consisted mainly of adenitis; disseminated forms were possible with immunodeficiency. Their evolution under specific treatments was comparable to that of tuberculosis. The presumed origin of the infection seemed to be environmental, possibly a water reservoir, and not due to human-to-human contagion.

Failure of dihydroartemisinin plus piperaquine treatment of falciparum malaria by under-dosing in an overweight patient.

BACKGROUND: Artemisinin-based combination therapy (ACT) introduced in the mid-1990s has been recommended since 2005 by the World Health Organization as first-line treatment against Plasmodium falciparum in all endemic countries. In 2010, the combination dihydroartemisinin-piperaquine (DP) was recommended for the treatment of uncomplicated P. falciparum malaria. DP is one of the first-line treatments used by the French army since 2013. CASE PRESENTATION: A case of P. falciparum clinical failure with DP at day 20 was described in a 104 kg French soldier deployed in Djibouti. He was admitted to hospital for supervision of oral treatment with DP [40 mg dihydroartemisinin (DHA) plus 320 mg piperaquine tetraphosphate (PPQ)]. This corresponded to a cumulative dose of 4.6 mg/kg DHA and 37 mg/kg PPQ in the present patient, which is far below the WHO recommended ranges. No mutation was found in the propeller domain of the Kelch 13 (k13) gene, which is associated with artemisinin resistance in Southeast Asia. Pfmdr1 N86, 184F, S1034 and N1042 polymorphisms and haplotype 72-76 CVIET for the pfcrt gene were found in the present case. There was no evidence of resistance to DP. CONCLUSION: This case confirms the risk of therapeutic failure with dihydroartemisinin-piperaquine by under-dosing in patients weighing more than 100 kg. This therapeutic failure with DP by under-dosing highlighted the importance of appropriate dosing guidelines and the need of research data (efficacy, pharmacokinetics and pharmacodynamics) in over-weight patient group.

Factors associated with malaria chemoprophylaxis compliance among French service members deployed in Central African Republic.

BACKGROUND: Malaria is a public health concern in the French armed forces, with 400-800 cases reported every year and three deaths in the past 2 years. However, lack of chemoprophylaxis (CP) compliance is often reported among service members. The aim of this study was to explore factors associated with CP compliance. METHODS: A retrospective study (1296 service members) was carried out among troops deployed in Central African Republic. Determinants of CP were collected by self-questionnaire. Socio-demographic variables, behavioural characteristics, belief variables, operational determinants such as troops in contact (TIC) and number of nights worked per week and peer-to-peer reinforcement were studied. Relationships between covariates and compliance were explored using logistic regressions (outcome: compliance as a dummy variable). RESULTS: Chemoprophylaxis compliance was associated with other individual preventive measures against mosquito bites (bed net use, OR (odds ratio) = 1.41 (95% CI [1.08-1.84]), and insecticide on clothing, OR = 1.90 ([1.43-2.51]) and malaria-related behaviours (taking chemoprophylaxis at the same time every day, OR = 2.37 ([1.17-4.78]) and taking chemoprophylaxis with food, OR = 1.45 ([1.11-1.89])). High perceived risk of contracting malaria, OR = 1.59 ([1.02-2.50]), positive perception of CP effectiveness, OR = 1.62 ([1.09-2.40]) and the practice of peer-to-peer reinforcement, OR = 1.38 ([1.05-1.82]) were also associated with better compliance. No association was found with TIC and number of nights worked. CONCLUSIONS: This study, which shows a positive relationship between peer-to-peer reinforcement and CP compliance, also suggests the existence of two main personality profiles among service members: those who seek risks and those who are health-conscious. Health education should be expanded beyond knowledge, know-how and motivational factors by using a comprehensive approach based on identification of health determinants, development of psychosocial skills and peer-to-peer reinforcement.

Epidemiological and entomological studies of a malaria outbreak among French armed forces deployed at illegal gold mining sites reveal new aspects of the disease's transmission in French Guiana.

BACKGROUND: In December 2010, a Plasmodium vivax malaria outbreak occurred among French forces involved in a mission to control illegal gold mining in French Guiana. The findings of epidemiological and entomological investigations conducted after this outbreak are presented here. METHODS: Data related to malaria cases reported to the French armed forces epidemiological surveillance system were collected during the epidemic period from December 2010 to April 2011. A retrospective cohort study was conducted to identify presumed contamination sites. Anopheles mosquitoes were sampled at the identified sites using Mosquito Magnet and CDC light traps. Specimens were identified morphologically and confirmed using molecular methods (sequencing of ITS2 gene and/or barcoding). Anopheles infections with Plasmodium falciparum and P. vivax were tested by both enzyme-linked immunosorbent assay and real-time PCR. RESULTS: Seventy-two P. vivax malaria cases were reported (three were mixed P. falciparum/P. vivax infections), leading to a global attack rate of 26.5% (72/272). Lack of compliance with vector control measures and doxycycline chemoprophylaxis was reported by patients. Two illegal gold mining sites located in remote areas in the primary forest were identified as places of contamination. In all, 595 Anopheles females were caught and 528 specimens were formally identified: 305 Anopheles darlingi, 145 Anopheles nuneztovari s.l., 63 Anopheles marajoara and 15 Anopheles triannulatus s.l. Three An. darlingi were infected by P. falciparum (infection rate: 1.1%) and four An. marajoara by P. vivax (infection rate: 6.4%). DISCUSSION: The main drivers of the outbreak were the lack of adherence by military personnel to malaria prevention measures and the high level of malaria transmission at illegal gold mining sites. Anopheles marajoara was clearly implicated in malaria transmission for the first time in French Guiana. The high infection rates observed confirm that illegal gold mining sites must be considered as high level malaria transmission areas in the territory. CONCLUSIONS: Illegal gold mining activities are challenging the control of malaria in French Guiana. Collaboration with neighbouring countries is necessary to take into account mobile populations such as gold miners. Malaria control strategies in the French armed forces must be adapted to P. vivax malaria and sylvatic Anopheles species.

Prosthetic joint infection caused by Pasteurella multocida: a case series and review of literature.

BACKGROUND: Pasteurella multocida is a well-recognized zoonotic agent following dog or cat bites or scratches. Nevertheless, prosthetic joint infection caused by P. multocida are rarely reported. METHOD: We report here a series of six cases of prosthetic joint infection caused by P. multocida managed at a referral centre for the treatment of bone and joint infection in southern France. We also reviewed the 26 cases reported in literature. RESULTS: The mean age of our cases was 74 years [±8.2, range 63-85]. In majority of our cases (5 cases) were associated with knee prostheses and one case with a hip prosthesis. Most of cases occurred after cat or dog scratches or licks or contact. Diagnoses of prosthetic joint infection caused by P. multocida were made by positive cultures of surgical biopsies or needle aspiration. Mean time delay between prosthetic joint implantation and infection onset was 7.6 years (±5.12 years, range 2-17). Local inflammation, which occurred in all six cases, was the most frequent clinical symptom, followed by pain in five cases, fever and swollen joints in four cases, and a fistula with purulent discharge inside the wound in two cases. The mean time of antibiotic therapy was 8 months. Surgical treatment with prosthesis removal was performed in three cases. Six of our cases were in remission without apparent relapse at 3 years after end of treatment. CONCLUSION: Prosthetic joint infections caused by P. multocida usually occur after animal scratches or bites, but can occasionally occur after a short animal lick. These infections are usually resulting from a contiguous infection and localized in the knee. An early antibiotic therapy after surgical debridement could avoid prosthetic withdrawal, notably in elderly patients. Patients with prosthetic joints should be warned that animals are potential sources of serious infection and urgent medical advice should be sought if they are bitten or scratched.

Rift Valley fever in kidney transplant recipient returning from Mali with viral RNA detected in semen up to four months from symptom onset, France, autumn 2015.

A 29-year-old kidney transplant recipient returning from Mali was diagnosed with Rift Valley fever (RVF) in France in autumn 2015. The patient was immunosuppressed due to his renal transplant. IgM and IgG specific to RVF virus (RVFV) were detected in cerebrospinal fluid and blood up to two months after symptom onset, whereas in urine, RVFV genomic RNA was detected by RT-PCR up to three months, and in semen up to four months post symptom onset.

Identification of initial severity determinants to predict arthritis after chikungunya infection in a cohort of French gendarmes.

BACKGROUND: The objective was to identify severity characteristics of initial chikungunya infection (CHIKV) stages associated with post-CHIKV arthritis and arthralgia. METHODS: French gendarmes exposed to the 2005-2006 CHIKV epidemic in Reunion Island who completed the 2006 (self-reporting acute and early chronic [median: 6 months] symptoms) and 2008 (Endpoint [median: 30 months]: self-perceived recovery and rheumatic disorders (RDs)) surveys were included. Multinomial logistic regression and multiple correspondence analysis (MCA) were used. Arthralgia was defined by joint pain and/or stiffness and arthritis by joint swelling in addition to pain and/or stiffness. RESULTS: In 2008, 124 (31.3%)/403 participants (101 CHIKV+/302 CHIKV-) reported arthralgia and 57 (14.1%) arthritis. The multivariate model kept CHIKV infection, comorbidity and acute stage depressed mood as independent prognostic factors for both arthralgia and arthritis, but found early chronic stage RD as the main determinant of the same RD two years later.The MCA performed with the 85 CHIKV + patients who answered the question on self-perceived recovery enabled the calculation of severity scores based on initial symptoms that were strongly associated with persistent arthritis and, to a lesser extent, to arthralgia in bivariate analyses. The MCA graph clearly distinguished arthritis as the only RD associated with early severity indicators represented by sick leave, joint swelling and depressed mood during the acute stage, and early chronification of arthritis and depressed mood. CONCLUSION: Initial CHIKV severity predicted recovery, with higher severity associated with arthritis and lower severity with arthralgia. More interestingly, specific markers of post-CHIKV arthritis, which can easily be used by clinicians for case management, were identified.

Chikungunya infection in returned travellers: results from the geosentinel network, 2005-2020.

BACKGROUND: Chikungunya is an important travel-related disease because of its rapid geographical expansion and potential for prolonged morbidity. Improved understanding of the epidemiology of travel-related chikungunya infections may influence prevention strategies including education and vaccination. METHODS: We analysed data from travellers with confirmed or probable chikungunya reported to GeoSentinel sites from 2005 to 2020. Confirmed chikungunya was defined as a compatible clinical history plus either virus isolation, positive nucleic acid test or seroconversion/rising titre in paired sera. Probable chikungunya was defined as a compatible clinical history with a single positive serology result. RESULTS: 1202 travellers (896 confirmed and 306 probable) with chikungunya were included. The median age was 43 years (range 0-91; interquartile range [IQR]: 31-55); 707 (58.8%) travellers were female. Most infections were acquired in the Caribbean (28.8%), Southeast Asia (22.8%), South Central Asia (14.2%) and South America (14.2%). The highest numbers of chikungunya cases reported to GeoSentinel were in 2014 (28.3%), 2015 (14.3%) and 2019 (11.9%). The most frequent reasons for travel were tourism (n = 592; 49.3%) and visiting friends or relatives (n = 334; 27.7%). The median time to presentation to a GeoSentinel site was 23 days (IQR: 7-52) after symptom onset. In travellers with confirmed chikungunya and no other reported illnesses, the most frequently reported symptoms included musculoskeletal symptoms (98.8%), fever/chills/sweats (68.7%) and dermatologic symptoms (35.5%). Among 917 travellers with information available, 296 (32.3%) had a pretravel consultation. CONCLUSIONS: Chikungunya was acquired by international travellers in almost 100 destinations globally. Vector precautions and vaccination where recommended should be integrated into pretravel visits for travellers going to areas with chikungunya or areas with the potential for transmission. Continued surveillance of travel-related chikungunya may help public health officials and clinicians limit the transmission of this potentially debilitating disease by defining regions where protective measures (e.g. pretravel vaccination) should be strongly considered.

Travel-associated diseases, Indian Ocean Islands, 1997-2010.

Data collected by the GeoSentinel Surveillance Network for 1,415 ill travelers returning from Indian Ocean islands during 1997-2010 were analyzed. Malaria (from Comoros and Madagascar), acute nonparasitic diarrhea, and parasitoses were the most frequently diagnosed infectious diseases. An increase in arboviral diseases reflected the 2005 outbreak of chikungunya fever.

A new challenge for hospitals in southeast France: monitoring local populations of Aedes albopictus to prevent nosocomial transmission of dengue or chikungunya.

Aedes albopictus was first identified in southern France in 2004, inducing an emerging risk for autochthonous transmission around imported cases of dengue or chikungunya, and also for mosquito-borne nosocomial transmission in hospitals. Aedes albopictus has been present in Marseille since September 2009 and in Aix-en-Provence since August 2010. Because of the possible admission of viremic patients with dengue or chikungunya in the hospitals of these cities, a mosquito survey was conducted in 2011 in 2 of the hospitals, with the use of mosquito traps. Aedes albopictus was detected with Eisenhans II traps and egg traps in both hospitals during the warm season.

Chikungunya: risks for travellers.

RATIONALE FOR REVIEW: Chikungunya outbreaks continue to occur, with changing epidemiology. Awareness about chikungunya is low both among the at-risk travellers and healthcare professionals, which can result in underdiagnosis and underreporting. This review aims to improve awareness among healthcare professionals regarding the risks of chikungunya for travellers. KEY FINDINGS: Chikungunya virus transmission to humans occurs mainly via daytime-active mosquitoes, Aedes aegypti and Aedes albopictus. The areas where these mosquitoes live is continuously expanding, partly due to climate changes. Chikungunya is characterized by an acute onset of fever with joint pain. These symptoms generally resolve within 1-3 weeks, but at least one-third of the patients suffer from debilitating rheumatologic symptoms for months to years. Large outbreaks in changing regions of the world since the turn of the 21st century (e.g. Caribbean, La Réunion; currently Brazil, India) have resulted in growing numbers of travellers importing chikungunya, mainly to Europe and North America. Viremic travellers with chikungunya infection have seeded chikungunya clusters (France, United States of America) and outbreaks (Italy in 2007 and 2017) in non-endemic countries where Ae. albopictus mosquitoes are present. Community preventive measures are important to prevent disease transmission by mosquitoes. Individual preventive options are limited to personal protection measures against mosquito bites, particularly the daytime-active mosquitos that transmit the chikungunya virus. Candidate vaccines are on the horizon and regulatory authorities will need to assess environmental and host risk factors for persistent sequelae, such as obesity, age (over 40 years) and history of arthritis or inflammatory rheumatologic disease to determine which populations should be targeted for these chikungunya vaccines. CONCLUSIONS/RECOMMENDATIONS: Travellers planning to visit destinations with active CHIKV circulation should be advised about the risk for chikungunya, prevention strategies, the disease manifestations, possible chronic rheumatologic sequelae and, if symptomatic, seek medical evaluation and report potential exposures.

Impaired quality of life after chikungunya virus infection: a 2-year follow-up study.

OBJECTIVES: To measure the frequency of and risk factors for rheumatic manifestations after chikungunya virus (CHIKV) infection and to assess their impact on quality of life (QoL). METHODS: In a cohort study among 509 cases diagnosed in France, demographic and clinical characteristics were collected at baseline, and QoL status by 36-item short-form health survey (SF-36), a short form of the Arthritis Impact Measurement Scales 2 (AIMS2-SF) and General Health Questionnaire (GHQ-12) at follow-up. SF-36 scores were compared with population norms. Factors associated with QoL were identified in multivariate linear regression models. RESULTS: A total of 391 (77%) patients participated (53.5% female, mean age 50.2 years). Median time from onset at follow-up was 23.4 months. Among 176 recovered patients, a shorter duration of symptoms was observed in younger age groups and male patients. The probability of full recovery at 1 year was 0.39. Those not recovered were older, had more comorbidities and a longer acute stage with joint swelling. Scores of physical and mental components of the SF-36 and GHQ-12 were low. The AIMS2-SF was affected mainly in symptoms, psychological and social dimensions. Recovered patients did not differ significantly from age- and gender-matched population SF-36 norms. Older age (P = 0.01-0.002) was associated with lower SF-36 scores. Other factors associated with lower SF-36, lower GHQ12 scores and higher AIMS2-SF dimensions were lack of recovery (P = 0.017 to <0.0001), presence of comorbidity (P = 0.005 to <0.0001) and a longer duration of acute stage (P = 0.047 to <0.0001). CONCLUSION: Medical follow-up with special attention to comorbidity providing information on possible chronic symptoms and giving support for potential depression and anxiety are recommended.

Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum.

BACKGROUND: The aim of the present work was to assess i) ex vivo activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 Plasmodium falciparum isolates from African countries, India and Thailand, and iii) in vitro cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN). METHODS: The susceptibility of the 181 P. falciparum isolates to the nine anti-malarial drugs was assessed using the standard 42-hours 3H-hypoxanthine uptake inhibition method. RESULTS: The IC50 values for PND ranged from 0.55 to 80.0 nM (geometric mean = 19.9 nM) and from 11.8 to 217.3 nM for PPQ (geometric mean = 66.8 nM). A significant positive correlation was shown between responses to PPQ and PND responses (rho = 0.46) and between PPQ and MDAQ (rho = 0.30). No significant correlation was shown between PPQ IC50 and responses to other anti-malarial drugs. A significant positive correlation was shown between responses to PND and MDAQ (rho = 0.37), PND and LMF (rho = 0.28), PND and QN (rho = 0.24), PND and AS (rho = 0.19), PND and DHA (rho = 0.18) and PND and CQ (rho = 0.16). All these coefficients of correlation are too low to suggest cross-resistance between PPQ or PND and the other drugs. CONCLUSIONS: In this study, the excellent anti-malarial activity of PPQ and PND was confirmed. The absence of cross-resistance with quinolines and artemisinin derivatives is consistent with the efficacy of the combinations of PPQ and DHA or PND and AS in areas where parasites are resistant to conventional anti-malarial drugs.

Role and Limits of COVID-19 Vaccines in the Delicate Transition from Pandemic Mitigation to Endemic Control.

The recent surge of COVID-19 related to the Omicron variant emergence has thrown a harsh light upon epidemic control in the near future. This should lead the scientific and medical community to question the long-term vaccine strategy for SARS-CoV-2 control. We provide here a critical point of view regarding the virological evolution, epidemiological aspects, and immunological drivers for COVID-19 control, including a vaccination strategy. Overall, we need more innovations in vaccine development to reduce the COVID-19 burden long term. The most adequate answer might be better cooperation between universities, biotech and pharmaceutical companies.

Determinants of Health-Related Quality of Life in Chronic Chikungunya Disease in Guadeloupe.

Chronic chikungunya disease is associated with a poor quality of life and a variety of symptoms, not restricted to the musculoskeletal system. Patients with chronic chikungunya disease in Guadeloupe were evaluated in order to identify the main factors determining the quality of life. Patients were followed up at a mean of 36 months after chikungunya infection, undergoing detailed clinical examination for musculoskeletal involvement, with assessment of subjective symptoms and the impact on mood, physical activity, and quality of life (SF12). Patients had extensive musculoskeletal involvement shown by tenderness in 9 ± 4 joints and stiffness in 5 ± 4 joints. SF12 physical and mental component scores showed a poor health-related quality of life. Measures of joint pain, stiffness, and inflammation contributed to impaired quality of life scores. In addition, fatigue and interrupted sleep appeared to be important predictors for physical aspects of quality of life. The emergence of anxiodepressive syndromes post-chikungunya infection was associated with both physical and mental component scores of SF12. These data confirm that musculoskeletal symptoms are not the only determinants of quality of life in chronic chikungunya disease. Follow-up of patients should include assessment and management of fatigue, poor sleep quality, and anxiodepressive syndromes.