Introduction
As the coronavirus disease 2019 (COVID-19) pandemic reaches South America, researchers
have already reported concerns about the impact that significant co-circulation of
the dengue viruses and COVID-19 could have on the health system [1–3]. In Singapore,
2 clinical cases consisted of dengue-like syndromes with thrombocytopenia and false
immunoglobulin M (IgM) positives with 2 different serological kits in patients who
were finally shown to have COVID-19 [4]. In addition to differential diagnosis, there
is always the possibility of coinfections by both COVID-19 and dengue virus, as was
recently described in Mayotte [5]. It is not yet known whether such coinfections will
lead to greater severity, but it should be a point of vigilance. Coinfections with
different pathogens may result in complex and unpredictable consequences on severity.
The literature suggests that co-infections with flu and dengue may be associated with
greater severity [6,7]. In French Guiana and the Amazonian region of Brazil, the coinfection
between malaria and dengue is not exceptional [8,9]. Arboviral infections (Tonate,
Mayaro) [10], Q fever [11], leptospirosis, influenza, Amazonian toxoplasmosis, and
primary HIV infection can be potential differential diagnoses during a dengue epidemic
[12]. The first 24 to 48 hours are important due to similar signs before the clinical
differentiation of the different diseases.
In April 2020, 7 years after the last epidemic, the Committee for Infectious and Emergent
Diseases officially declared a dengue epidemic (dengue virus 1 [DENV-1] and 2) on
the Maroni River, in the Kourou area, and in the Cayenne Area [13]. This occurs simultaneously
with the COVID-19 pandemic (Fig 1), and the perspective of joint epidemics has several
complex collateral consequences.
10.1371/journal.pntd.0008426.g001
Fig 1
Dengue and COVID-19 data: French Guiana, January–April 2020.
COVID-19, coronavirus disease 2019.
Is it COVID-19 or dengue?
Contextual elements are surely important to orient clinicians. While some clinical
signs may point to COVID-19 or dengue in case series, at the individual patient scale,
the imperfect positive predictive value and clinical variability do not guarantee
a diagnosis of certainty (Table 1). Thus, some studies report 25% of patients with
confirmed dengue having a cough and 20% with upper respiratory tract symptoms [14].
Similarly, COVID-19 may manifest itself as fever with muscle and joint pains without
respiratory symptoms, especially in infants [15–17]. Thus, most patients must be explored
for both diseases.
10.1371/journal.pntd.0008426.t001
Table 1
COVID-19 and dengue fever similarities and differences.
COVID-19
Dengue
Symptoms and biological findings
Fever
+++
+++
Headache
++
+++
Retro-orbital pain
a
++
Asthenia
+
++
Rash
+
++
Purpura
a
++
Myalgia/arthralgia
+
++
Dyspnea
b
++
Anorexia
+
+
Cough
b
+++
+
Chest pain
b
++
Cyanosis
b
+
Pharyngitis
b
++
++
Rhinorrhea
b
+
Sneezing
b
+
Anosmia, ageusia
b
+++
± (dysgueusia)
Diarrhea
+
+
Nausea/vomiting
+
+
Persistent vomiting
a
+*
Abdominal pain
a
++*
Consciousness alteration
+
+*
Agitation
+*
+*
Biology
CRP
b
++*
Procalcitonin
b
+*
Leukocytes
b
↓
Neutrophils
b
Relative ↑
Relative ↓
Lymphocytes
b
Relative ↓
Relative ↓
Platelets
↓*
↓
Ferritin
↑*
↑*
Hemoglobin
↑*
Serum protein/albumin
↓*
↓*
O2 saturation
↓*
↓*
PO2
↓*
↓*
ASAT/ALAT
↑
↑
LDH
↑*
↑*
D-dimers
b
↑*
Troponin
b
↑*
#
Sodium
↓*
↓*
Potassium
↓*
Calcium
↓*
aIndicates more discriminating criteria DENGUE.
bIndicates more discriminating criteria COVID-19.
*Prognostic value.
#The American College of Cardiology recommends not to prescribe it unless suspected
of infarction.
Abbreviations: ALAT, alanine amino transferase; ASAT, aspartate amino transferase;
COVID-19, coronavirus disease 2019; CRP, C-reactive protein; LDH, lactate dehydrogenase
However, given the safety constraints linked to COVID-19, any nonurgent febrile patient
must be seen and tested in a special sector where great precautions are taken to avoid
the risk of transmission [18]. This creates organizational bottlenecks. Because of
this great disruption in the organization of care, until recently it was only after
receiving the results (24–48 hours for negative results) that further explorations
were performed, which for a while led to potentially dangerous diagnostic delays in
patients with dengue. Indeed, the critical period is between 3 and 8 days, usually
at the time of defervescence, and a 48-hour delay in this context can be a loss of
chance for patients with dengue, as this disease may be potentially lethal as well
[19,20]. For nonfebrile patients with rhinopharyngitis and cough, dengue may not be
a first-line diagnosis.
In the context of cocirculation of 2 potentially fatal viruses, it is key to enable
a combined diagnosis (COVID-19–dengue) for ambulatory patients and at least complete
blood count, liver enzymes, C-reactive protein, serum protein, creatinine, and electrolytes.
For patients who require hospitalization, the logistical problem is less complicated,
and all the necessary samples are taken. In a context where hospital beds are sparse
and patients are mostly confined at home with telemedicine follow-up, dyspnea, cyanosis,
impaired consciousness, fainting, shock, hemorrhagic signs, and jaundice—initially
or during follow-up—should be points of vigilance in order to hospitalize patients
if needed.
Telemedicine or normal consultation?
Given the potential risks of infectious diseases in pregnancy, and the difficulties
to evaluate small children, infants and pregnant women should preferably have normal
consultations. Patients with signs of severity requiring hospitalization are treated
in the hospital with the necessary precautions until the diagnosis is made. For other
patients, they can consult the hospital in a specific location for diagnosis and follow-up
of fever during COVID-19 + dengue epidemics. For patients using teleconsultations,
paraclinical tests should be performed at one of the COVID-19 + dengue diagnostic
centers [21]. Follow-up can be monitored by regular teleconsultations, with the possibility,
if necessary, of home visits by nurses or a pool of doctors equipped with personal
protective equipment (PPE) to check the constants and collect samples.
Other differential diagnoses?
The current differential diagnoses in French Guiana are as follows: In a context of
respiratory signs and symptoms, Q fever, usual respiratory pathogens such as Streptococcus
pneumoniae and Mycoplasma pneumoniae, influenza, leptospirosis, and Amazonian toxoplasmosis;
dengue-like clinical presentations may also be caused by other arboviruses such as
Tonate virus and Mayaro virus (French Guiana reports no case of chikungunya virus
infection from early 2016 and no case of Zika virus infection from early 2017) [22],
malaria, Q fever, leptospirosis, salmonellosis, and HIV primary infection [10,12,23,24].
This list will vary between regions. The objectives of paraclinical explorations are
2-fold: to make the differential diagnosis and to look for signs of severity (white
blood cell and platelet counts, C-reactive protein, serum electrolytes, aspartate
amino transferase, alanine amino transferase, bilirubin, prothrombin time, activated
thromboplastin time, and lactate dehydrogenase [LDH]). According to the context and
clinical presentation, physicians may prescribe a malaria test, blood and urine cultures,
serologies, or molecular diagnosis of differential diagnoses.
What is the impact of social distancing on dengue epidemics?
In French Guiana, with social distancing, vector control has been scaled back by only
relying on vehicle spraying of neighborhoods with deltamethrin to attempt—in a context
of widespread insecticide resistance—to reduce vector numbers. However, intra-domiciliary
or compound interventions to destroy larvae or inspect for breeding places, or in-house
spraying, have been interrupted. Maintenance of public spaces and gardens and collection
of potential water receptacles have been drastically reduced. All this arguably has
the potential to give an edge to the dengue fever vectors, Aedes aegypti. Population
movements and the frequency of interactions are major drivers of epidemics [25]. Social
distancing, while considered to double intra-domiciliary COVID-19 transmission, greatly
reduces transmission at the population level [26]. There is also a close link between
travel and dengue epidemics [27]. In French Guiana, daily airline connections between
Guadeloupe, Martinique, and French Guiana are historical drivers of dengue virus circulation
[28]. Currently, in French Guiana transmission has increased during social distancing,
which was implemented simultaneously with the second rainy season. It is therefore
difficult to disentangle the respective contributions of rainfall and suboptimal mosquito
control measures due to social distancing. Transmission depends on the frequency of
mosquito bites, and infection incidence in the human and mosquito populations is almost
independent of the duration of contacts [27]. Mosquitoes are locally mobile but only
travel short distances, usually far less than infected humans who can extend the epidemic
potential. Modeling studies on the relation between population movements and dengue
suggest that increased population movements should indeed increase the risk of epidemic
[29,30]. If the mosquito population was not uniformly distributed, the transmission
potential of dengue at the metapopulation level would be determined by the size of
the largest subpopulation and would be reduced by stronger human-mediated connectivity
between vector populations. The extinction of the dengue virus epidemic is less likely
when increased human movement enhances the rescue effect. Thus, modeling suggests
that infection hubs and reservoirs can be locations people visit frequently, but briefly,
and the relative importance of human and mosquito populations in maintaining dengue
depends on the distribution of the vector population and the variability in human
travel patterns.
Does COVID-19 social distancing have the potential to increase dengue morbidity?
With the lockdown, people stay home, and the risk of dengue infection may increase
as A. aegypti, the vector of dengue virus, lays its eggs on the walls of water-filled
containers in the house and its surroundings. Moreover, many persons are afraid to
go to the hospital or to consult health professionals because they fear that other
patients or health professionals have COVID-19. In French Guiana, despite a limited
number of cases (97 on April 21, 2020), the number of consultations has greatly declined
in part because nonurgent health problems are postponed but perhaps because of this
fear of contamination. Moreover, given the safety constraints linked to COVID-19,
any nonurgent febrile patient must be seen and tested in a special sector where great
precautions are taken to avoid the risk of transmission. Because of this great disruption
in the organization of care, until recently it was only after receiving the results
(24–48 hours for negative results) that further explorations were performed, which
for a while led to potentially dangerous diagnostic delays in patients with dengue.
PPE and reagents
Although there have already been organizational complications capable of affecting
the quality of care and vector control, due to the co-circulation of viruses there
are additional aspects that are worrisome. In a context of global depletion of PPE,
the increase of dengue circulation with around 150 (for the moment) suspected dengue
patients per week (Fig 1) in a context of COVID-19 circulation will lead to a significant
increase in PPE use because, with COVID-19 circulation, febrile patients require special
protection until COVID-19 has been ruled out. This will further aggravate pressure
on stocks that are already insufficient and challenging to replenish. Furthermore,
the COVID-19 epidemic has led to global shortages in certain laboratory reagents.
Hence, molecular diagnosis of COVID-19 and dengue requires extraction kits and enzymes
that are the same and thus accelerate the depletion of stocks with uncertainties as
to when it will be possible to restock. Thus, to spare reagents, nonstructural antigen
1 (NS-1) rapid tests are used despite their imperfect sensitivity, assuming their
positive predictive value is good during an epidemic. Only negative NS-1 results are
checked with real-time PCR and serology.
Another tension for the system is that health workers may be incapacitated by either
disease. For COVID-19, it has been shown in China, Italy, and the US that a substantial
proportion of health workers were infected by COVID-19, presumably more in emergency
services [31,32]. In Mayotte, a French Island in the southwestern Indian Ocean, almost
20% of the more than 200 patients infected with COVID-19 are health workers. In French
Guiana, several emergency physicians have already been infected [33]. Moreover, given
the rapid turnover of health professionals rotating from mainland France, a large
proportion of the staff is not immune to dengue, and past epidemics have often affected
a significant proportion of the hospital workforce, another potential source of tension.
What can we do now?
The population should be well aware of both dengue and COVID-19 and should be informed
about prevention measures. Regarding vector control, health promotion should encourage
populations to look out for potential vector breeding places and protect themselves
from mosquito bites. Local authorities should be very vigilant and activate strategic
services essential to vector control (waste management, maintenance of public spaces,
intra-domiciliary interventions, notably around cases). Regarding COVID-19, testing
of suspected cases should expand (it has been hampered by logistical constraints and
insufficient supplies of swabs and reagents), and aggressive contact tracing and isolation
should continue. Diagnosis of febrile patients should be organized to allow diagnosing
of both dengue and COVID-19 without delays due to COVID-19 constraints. Hospitals,
which have been radically reorganized to accommodate a surge of COVID-19 patients,
should plan for severe dengue beds. Patients should remain under mosquito nets, to
avoid infecting other mosquitoes. Finally, although during a single epidemic specific
syndromes have good positive predictive value and do not always require biological
confirmation, in this case, because of the co-circulation and the complicated collateral
consequences, diagnostic confirmation seems mandatory throughout the epidemic, which
will use more resources.
What will happen in the months ahead?
The last dengue epidemic lasted a year (2012 week 40 to 2013 week 42) and 5 months
with 500–700 weekly clinical cases reported by the sentinel network for a population
of 260,000 [34]. The impact of social distancing relaxation on population movements
and the epidemic is hard to predict, but it could further accelerate the circulation
of the virus in mosquito populations. For COVID-19, for the moment the surge has not
happened due to the early implementation of social distancing, border closure, and
cancelation of most air traffic. Most initial cases were imported with secondary transmission
clusters around imported cases. However, as social distancing relaxes in the weeks
ahead and flights from France and French Caribbean (Martinique and Guadeloupe) resume,
the potential for reigniting the epidemic will increase. Authorities will need to
be very aggressive on contact tracing and vigilant on testing and tracking arriving
passengers. With a single international airport this seems very feasible. However,
a more difficult task is to control borders with Suriname and especially with Brazil.
These borders largely consist of Amazonian forest and are difficult to control, as
shown by the massive influx of illegal goldminers from Brazil in French Guiana. As
the Brazilian president resists social distancing, there are risks of importing cases
through the interior villages, a concern that also affects other neighboring countries.
Furthermore, the state of Amapá, neighboring French Guiana, seems to be currently
one of the most impacted in Brazil in terms of the number of COVID-19 patients in
proportion to its population. The incidence on May 21 was 613.4 per 100,000 inhabitants,
and fatalities were 17.9 per 100,000 inhabitants [35]. Several large clusters have
appeared on the border with Brazil, which has now become the most active site for
COVID-19. Suriname, a country bordering French Guiana, has so far registered 565 suspected
cases, 11 people confirmed positive for COVID-19, and 1 death, according to the results
communicated by the Surinamese authorities in May [36]. In this context, a simultaneous
dengue epidemic will be a major problem for the healthcare systems in the region,
and beyond.