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.

Origin of COVID-19: Dismissing the Mojiang mine theory and the laboratory accident narrative.

The origin of SARS-CoV-2 is still the subject of a controversial debate. The natural origin theory is confronted to the laboratory leak theory. The latter is composite and comprises contradictory theories, one being the leak of a naturally occurring virus and the other the leak of a genetically engineered virus. The laboratory leak theory is essentially based on a publication by Rahalkar and Bahulikar in 2020 linking SARS-CoV-2 to the Mojiang mine incident in 2012 during which six miners fell sick and three died. We analyzed the clinical reports. The diagnosis is not that of COVID-19 or SARS. SARS-CoV-2 was not present in the Mojiang mine. We also bring arguments against the laboratory leak narrative.

Lessons learned from the investigation of a COVID-19 cluster in Creil, France: effectiveness of targeting symptomatic cases and conducting contact tracing around them.

BACKGROUND: This study presents the methods and results of the investigation into a SARS-CoV-2 outbreak in a professional community. Due to the limited testing capacity available in France at the time, we elaborated a testing strategy according to pre-test probability. METHODS: The investigation design combined active case finding and contact tracing around each confirmed case with testing of at-risk contact persons who had any evocative symptoms (n = 88). One month later, we performed serology testing to test and screen symptomatic and asymptomatic cases again (n = 79). RESULTS: Twenty-four patients were confirmed (14 with RT-PCR and 10 with serology). The attack rate was 29% (24/83). Median age was 40 (24 to 59), and the sex ratio was 15/12. Only three cases were asymptomatic (= no symptoms at all, 13%, 95% CI, 3-32). Nineteen symptomatic cases (79%, 95% CI, 63-95) presented a respiratory infection, two of which were severe. All the RT-PCR confirmed cases acquired protective antibodies. Median incubation was 4 days (from 1 to 13 days), and the median serial interval was 3 days (0 to 15). We identified pre-symptomatic transmission in 40% of this cluster, but no transmission from asymptomatic to symptomatic cases. CONCLUSION: We report the effective use of targeted testing according to pre-test probability, specifically prioritizing symptomatic COVID-19 diagnosis and contact tracing. The asymptomatic rate raises questions about the real role of asymptomatic infected people in transmission. Conversely, pre-symptomatic contamination occurred frequently in this cluster, highlighting the need to identify, test, and quarantine asymptomatic at-risk contact persons (= contact tracing). The local lockdown imposed helped reduce transmission during the investigation period.

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.

Travel-associated chikungunya acquired in Myanmar in 2019.

Eighteen cases of chikungunya virus infection in travellers returning from Myanmar were reported to the GeoSentinel Surveillance Network, its subnetwork EuroTravNet and TropNet in 2019, reflecting an ongoing local outbreak. This report reinforces the importance of travellers as sentinels of emerging arboviral outbreaks and highlights the importance of vigilance for imported cases, due to the potential for dissemination of the virus into areas with competent local vectors and conducive environmental conditions.

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.

Measles, the need for a paradigm shift.

Measles vaccination schedules and targets of herd immunity have been designed according to the paradigm that the vaccine is as protective as natural infection, and the virus has remained of a single serotype over many decades. As a result, ongoing measles resurgence is mostly attributed to gaps in immunization. Using official data, we investigated the correlation between the rate of vaccine coverage reported and aggregated at the national level, and the incidence of cases. We discussed the limits of this indicator considered in isolation. We provide a literature overview of measles vaccine efficacy and failures. We questioned whether measles strains could escape the vaccine. Immunization tools and strategies for measles control deserve to be optimized in the current context.

Increased risk of chikungunya infection in travellers to Thailand during ongoing outbreak in tourist areas: cases imported to Europe and the Middle East, early 2019.

We report nine travellers with confirmed chikungunya virus infection, returning from tourist areas of Thailand to Sweden, Switzerland, the United Kingdom, Romania, Israel and France, diagnosed in January and February 2019. These sentinel tourists support the intensification of chikungunya virus circulation in Thailand and highlight the potential for importation to areas at risk of local transmission.

Tracking Rift Valley fever: From Mali to Europe and other countries, 2016.

On 16 September 2016, the World Health Organization confirmed a Rift Valley fever (RVF) outbreak in Niger. Epidemiological surveillance was reinforced among the French Armed Forces deployed in Niger and bordering countries: Chad, Mali and Burkina Faso. On 26 October, a probable case of RVF was reported in a service member sampled in Mali 3 weeks earlier. At the time the result was reported, the patient was on vacation on Martinique. An epidemiological investigation was conducted to confirm this case and identify other cases. Finally, the case was not confirmed, but three suspected cases of RVF were confirmed using serological and molecular testing. RVF viral RNA was detectable in whole blood for 57 and 67 days after onset of symptoms for two cases, although it was absent from plasma and serum. At the time of diagnosis, these cases had already returned from Mali to Europe. The infectivity of other arboviruses in whole blood has already been highlighted. That RVF virus has been detected in whole blood that long after the onset of symptoms (67 days) raises the question of its potential prolonged infectivity. Because of exposure to tropical infectious diseases during deployment, military populations could import emerging pathogens to Europe.

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.

Long-Read Sequencing and De Novo Genome Assembly Pipeline of Two Plasmodium falciparum Clones (Pf3D7, PfW2) Using Only the PromethION Sequencer from Oxford Nanopore Technologies without Whole-Genome Amplification.

Antimalarial drug resistance has become a real public health problem despite WHO measures. New sequencing technologies make it possible to investigate genomic variations associated with resistant phenotypes at the genome-wide scale. Based on the use of hemisynthetic nanopores, the PromethION technology from Oxford Nanopore Technologies can produce long-read sequences, in contrast to previous short-read technologies used as the gold standard to sequence Plasmodium. Two clones of P. falciparum (Pf3D7 and PfW2) were sequenced in long-read using the PromethION sequencer from Oxford Nanopore Technologies without genomic amplification. This made it possible to create a processing analysis pipeline for human Plasmodium with ONT Fastq only. De novo assembly revealed N50 lengths of 18,488 kb and 17,502 kb for the Pf3D7 and PfW2, respectively. The genome size was estimated at 23,235,407 base pairs for the Pf3D7 clone and 21,712,038 base pairs for the PfW2 clone. The average genome coverage depth was estimated at 787X and 653X for the Pf3D7 and PfW2 clones, respectively. This study proposes an assembly processing pipeline for the human Plasmodium genome using software adapted to large ONT data and the high AT percentage of Plasmodium. This search provides all the parameters which were optimized for use with the software selected in the pipeline.

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.

Monkeypox clinical disease: Literature review and a tool proposal for the monitoring of cases and contacts.

The human monkeypox disease has mainly been described in Western and Central Africa. Since May 2022, the monkeypox virus has been spreading worldwide in a new epidemiological pattern, where cases result from person-to-person transmission, and develop clinically milder or less typical illness than during previous outbreaks in endemic areas. The newly-emerging monkeypox disease needs to be described over the long term, to improve cases definitions, to implement prompt control measures against epidemics, and to provide supportive care. Hence, we first conducted a review of historical and recent outbreaks to define the full clinical spectrum of the monkeypox disease and its course known so far. Then, we built a self-administrated questionnaire collecting daily symptoms of the monkeypox infection to follow cases and their contacts, even remotely. This tool will assist in the management of cases, the surveillance of contacts, and the conduct of clinical studies.

Clinical and Epidemiological Changes in French Soldiers After Deployment: Impact of Doxycycline Malaria Prophylaxis on Body Weight.

BACKGROUND: Antibiotics are growth promotors used in animal farming. Doxycycline (DOXY) is a tetracycline antibiotic taken daily and continued 1 month after return to protect against malaria during travel and deployment in endemic areas. We evaluated DOXY impact on body weight in military international travelers. MATERIEL AND METHODS: A prospective cohort analysis was conducted in 2016-2018, recruiting 170 French soldiers before a 4-month assignment overseas. Many clinical data including anthropometric measures by an investigator were collected before and after deployment. Weight gain was defined by an increase of 2% from baseline. The study protocol was supported by the French Armed Forces Health Services and approved by the French ethics committee (IRB no. 2015-A01961-48, ref promoter 2015RC0). Written, informed consent was obtained with signature from each volunteer before inclusion. RESULTS: After deployment, 84 soldiers were followed up. Overall, 38/84 (45%) were deployed to Mali with DOXY malaria prophylaxis, and others were deployed to Iraq or Lebanon without malaria prophylaxis according to international recommendations. Body weight increased in 24/84 (30%), of whom 14/24 (58%) were exposed to DOXY. In bivariate analysis, DOXY had a positive but not significant effect on weight gain (P-value = .4). In the final logistic regression model (Fig. 3), weight gain after deployment positively correlated with an increase in waist circumference (odds ratio [OR] 1.23 with 95% CI [1.06-1.47]) suggesting fat gain; with sedentary work (OR 5.34; 95% CI [1.07-31.90]); and with probiotic intake (OR 5.27; 95% CI [1.51-20.40]). Weight impact of probiotics was more important when associated with DOXY intake (OR 6.86; 95% CI [1.52-38.1]; P-value = .016). CONCLUSIONS: Doxycycline (DOXY) malaria prophylaxis during several months did not cause significant weight gain in soldiers. Further studies are required in older and less sportive traveling populations, and to investigate a cumulative effect over time and recurrent DOXY exposure. Doxycycline (DOXY) may enhance other growth-promoting factors including fatty food, sedentariness, and strain-specific probiotics contained in fermented dairy products which are also used as growth promotors.

Impact, healthcare utilization and costs of travel-associated mosquito-borne diseases in international travellers: a prospective study.

BACKGROUND: International travellers frequently acquire infectious diseases whilst travelling, yet relatively little is known about the impact and economic burden of these illnesses on travellers. We conducted a prospective exploratory costing study on adult returning travellers with falciparum malaria, dengue, chikungunya or Zika virus. METHODS: Patients were recruited in eight Travel and Tropical Medicine clinics between June 2016 and March 2020 upon travellers' first contact with the health system in their country of residence. The patients were presented with a structured 52-question self-administered questionnaire after full recovery to collect information on patients' healthcare utilization and out-of-pocket costs both in the destination and home country, and about income and other financial losses due to the illness. RESULTS: A total of 134 patients participated in the study (malaria, 66; dengue, 51; chikungunya, 8; Zika virus, 9; all fully recovered; median age 40; range 18-72 years). Prior to travelling, 42% of patients reported procuring medical evacuation insurance. Across the four illnesses, only 7% of patients were hospitalized abroad compared with 61% at home. Similarly, 15% sought ambulatory services whilst abroad compared with 61% at home. The average direct out-of-pocket hospitalization cost in the destination country (USD $2236; range: $108-$5160) was higher than the direct out-of-pocket ambulatory cost in the destination country (USD $327; range: $0-$1560), the direct out-of-pocket hospitalization cost at home (USD $35; range: $0-$120) and the direct out-of-pocket ambulatory costs at home (US$45; range: $0-$192). Respondents with dengue or malaria lost a median of USD $570 (Interquartile range [IQR] 240-1140) and USD $240 (IQR 0-600), respectively, due to their illness, whilst those with chikungunya and Zika virus lost a median of USD $2400 (IQR 1200-3600) and USD $1500 (IQR 510-2625), respectively. CONCLUSION: Travellers often incur significant costs due to travel-acquired diseases. Further research into the economic impact of these diseases on travellers should be conducted.