Seroprevalence of dengue, Japanese encephalitis and Zika among long-term expatriates in Thailand.

BACKGROUND: Travel to Southeast Asia increases the likelihood of acquiring mosquito-borne Flavivirus infections such as dengue (DENV), Japanese encephalitis (JEV) and Zika viruses (ZIKV). Expatriates are long-term travellers who have a higher risk of mosquito-borne illness at their destination country. The purpose of this study was to evaluate the seroprevalence of DENV, JEV and ZIKV infections and the determinants contributing to seropositivity among expatriates living in Thailand. METHODS: A cross-sectional study was performed from December 2017 to February 2020. Expatriates from non-Flavivirus endemic countries were recruited. 5 mL of blood was collected for DENV 1-4, JEV and ZIKV antibody testing by plaque reduction neutralization test (PRNT50). Individuals with vaccination histories or diagnoses for dengue, Japanese encephalitis, yellow fever and tick-borne encephalitis were excluded. RESULTS: Among 254 participants, most participants (83.1%) were male, the mean age was 65 years and the median duration of stay in Thailand was 6 years. Seroprevalence rate of any Flavivirus, non-specific DENV, DENV1-4, JEV and ZIKV were 34.3, 30.7, 20.5, 18.1, 18.9, 10.6, 4.7 and 2.8%, respectively. The presence of neutralizing antibodies against DENV1-4 positively correlates with the duration of stay in Thailand. DENV seropositivity was associated with living in urban areas (aOR 2.75, 95% CI 1.36-5.57). Expatriates were unlikely to have detectable anti-JEV antibodies regardless of time spent in a JEV-endemic area. No risk factors were identified that were significantly associated with JEV or ZIKV seropositivity. Only 48.4% received pre-travel counselling services, while only 18.9% visited a travel medicine specialist. CONCLUSIONS: A high proportion (34.3%) of long-term expatriates living in Thailand were seropositive for flavivirus, mainly from dengue (30.7%). To minimize risk, travel medicine practitioners should provide adequate pre-travel health risk information on mosquito-borne flavivirus infection and offer advice on mosquito bite prevention strategies. Dengue vaccine might be considered in high-risk travellers such as long-term expatriate.

The silent, rapidly unfolding threat of mpox spread via international travel to Southeast Asia: Are we ready?

The 2022 mpox (monkeypox) outbreak has been surprisingly large and has raised several novel questions about this disease. New information, such as atypical clinical manifestations and transmission via sexual activities, have been identified. These pose a potential risk of widespread outbreaks due to unusual clinical manifestations and failure to consider mpox as a diagnosis by physicians and the sexual behaviours of some tourists in Southeast Asia. Since Southeast Asia is a popular tourist destination, there is substantial potential for the silent spread of mpox in this region. Consequently, there is an urgent need for effective surveillance measures at points of entry of international travelers to identify suspected cases and their close contacts in order to limit the spread of mpox in Southeast Asia.

Concurrent Infection with SARS-CoV-2 and Orientia tsutsugamushi during the COVID-19 Pandemic in the Maldives.

The COVID-19 pandemic was the worst public-health crisis in recent history. The impact of the pandemic in tropical regions was further complicated by other endemic tropical diseases, which can cause concurrent infections along with COVID-19. Here, we describe the clinical course of a patient with concurrent COVID-19 and scrub typhus infection. The patient's de-identified clinical data were retrieved retrospectively. The patient had progressive breathlessness at the time of presentation and was hospitalized for COVID-19. Respiratory examination revealed dyspnea, tachypnea, and coarse crepitations bilaterally over the entire lung field. Oxygenation was impaired, and a PaO2/FiO2 ratio of 229 suggested acute respiratory distress syndrome. Laboratory tests indicated leukocytosis, thrombocytopenia, ferritinemia, hypoalbuminemia, and transaminitis. Upon revaluation for persistent fever, physical examination revealed an eschar in the right antecubital fossa. Serology further confirmed scrub typhus, with IgM and IgG antibody positivity. A remarkable clinical recovery was achieved with doxycycline. The COVID-19 pandemic might have masked endemic tropical diseases. Clinicians working in endemic regions must always consider common tropical diseases that may present as a co-infection, as in our case. Travel and exposure history are critical guides for narrowing down a differential diagnosis. Early diagnosis and treatment can prevent complications.

A Fatal Case of Native Valve Endocarditis with Multiple Embolic Phenomena and Invasive Methicillin-Resistant Staphylococcus aureus Bacteremia: A Case Report from the Maldives.

Infective endocarditis (IE) is a life-threatening condition caused by infection within the endocardium of the heart and commonly involves the valves. The subsequent cascading inflammation leads to the appearance of a highly friable thrombus that is large enough to become lodged within the heart chambers. As a result, fever, fatigue, heart murmurs, and embolization phenomena may be seen in patients with IE. Embolization results in the seeding of bacteria and obstruction of circulation, causing cell ischemia. Of concern, bacteria with the potential to gain pan-drug resistance, such as methicillin-resistant Staphylococcus aureus (MRSA), are increasingly being identified as the causative agent of IE in hospitals and among intravenous drug abusers. We retrospectively reviewed de-identified clinical data to summarize the clinical course of a patient with MRSA isolated using an automated blood culture system. At the time of presentation, the patient showed a poor consciousness level, and the calculated Glasgow scale was 10/15. A high-grade fever with circulatory shock indicated an occult infection, and a systolic murmur was observed with peripheral signs of embolization. This case demonstrated the emerging threat of antimicrobial resistance in the community and revealed clinical findings of IE that may be helpful to clinicians for the early recognition of the disease. The management of such cases requires a multi-specialty approach, which is not widely available in small-island developing states such as the Maldives.

A Case Report of Secondary Syphilis Co-Infected with Measles: A Diagnostic Dilemma with Fever and Rash.

Fever and rash as manifestations of infection by microorganisms are collectively known as febrile exanthem. Since viruses are more frequently associated with fever and rash, these symptoms are thus impetuously termed viral exanthem. However, bacteria represent a frequently overlooked infectious etiology causing rash in humans. In addition, certain microbes may exhibit pathognomonic features that erupt during illness and facilitate clinical diagnosis. Conversely, coinfections often obscure the clinical characteristics of the primary disease and further challenge clinicians attempting to reach a diagnosis. We retrospectively looked at de-identified clinical data of a patient who presented to the Hospital for Tropical Diseases in Bangkok in July 2019 with complaints of fever and rash. The case involved a 35-year-old who presented with a 3-day history of fever, respiratory symptoms, myalgia, conjunctivitis, diarrhea, and a generalized maculopapular rash. On examination, the patient was febrile, tachycardic, and tachypneic, with a mean arterial pressure of 95 mmHg. A differential white blood cell count showed: leukocytes, 5800/µL; neutrophils, 4408/µL; lymphocytes, 406/µL; and platelets, 155,000/µL. Striking findings involving the integumentary system included Koplik's spots and generalized maculopapular rash. Further serology revealed positive immunoglobulin (Ig)M and IgG for both measles and rubella virus, including reactive serology for Treponema pallidum. Here we describe the clinical course and management of this patient.

Spread of a Novel Indian Ocean Lineage Carrying E1-K211E/E2-V264A of Chikungunya Virus East/Central/South African Genotype across the Indian Subcontinent, Southeast Asia, and Eastern Africa.

The Indian Ocean Lineage (IOL) of the chikungunya virus (CHIKV) East/Central/South African (ECSA) genotype, which originated in Kenya, spread to the Indian ocean and the Indian subcontinent, and then expanded through Southeast Asia in the previous decade. It carried an adaptive mutation E1-A226V, which enhances CHIKV replication in Aedes albopictus. However, the IOL CHIKV of the most recent outbreaks during 2016-2020 in India, Pakistan, Bangladesh, the Maldives, Myanmar, Thailand, and Kenya lacked E1-A226V but carried E1-K211E and E2-V264A. Recent CHIKV genome sequences of the Maldives and Thailand were determined, and their phylogenetic relationships were further investigated together with IOL sequences reported in 2004-2020 in the database. The results showed that the ancestral IOLs diverged to a sub-lineage E1-K211E/E2-V264A, probably in India around 2008, and caused sporadic outbreaks in India during 2010-2015 and in Kenya in 2016. The massive expansion of this new sub-lineage occurred after the acquisition of E1-I317V in other neighboring and remote regions in 2014-2020. Additionally, the phylogenetic tree indicated that independent clades formed according to the geographical regions and introduction timing. The present results using all available partial or full sequences of the recent CHIKVs emphasized the dynamics of the IOL sub-lineages in the Indian subcontinent, Southeast Asia, and Eastern Africa.

Plasmodium vivax gametocytes and transmission.

Malaria elimination means cessation of parasite transmission. At present, the declining malaria incidence in many countries has made elimination a feasible goal. Transmission control has thus been placed at the center of the national malaria control programs. The efficient transmission of Plasmodium vivax from humans to mosquitoes is a key factor that helps perpetuate malaria in endemic areas. A better understanding of transmission is crucial to the success of elimination efforts. Biological delineation of the parasite transmission process is important for identifying and prioritizing new targets of intervention. Identification of the infectious parasite reservoir in the community is key to devising an effective elimination strategy. Here we describe the fundamental characteristics of P. vivax gametocytes - the dynamics of their production, longevity, and the relationship with the total parasitemia - as well as recent advances in the molecular understanding of parasite sexual development. In relation to malaria elimination, factors influencing the human infectivity and the current evidence for a role of asymptomatic carriers in transmission are presented.

Development of a Dengue Virus Serotype-Specific Non-Structural Protein 1 Capture Immunochromatography Method.

Four serotypes of dengue virus (DENV), type 1 to 4 (DENV-1 to DENV-4), exhibit approximately 25-40% of the difference in the encoded amino acid residues of viral proteins. Reverse transcription of RNA extracted from specimens followed by PCR amplification is the current standard method of DENV serotype determination. However, since this method is time-consuming, rapid detection systems are desirable. We established several mouse monoclonal antibodies directed against DENV non-structural protein 1 and integrated them into rapid DENV detection systems. We successfully developed serotype-specific immunochromatography systems for all four DENV serotypes. Each system can detect 104 copies/mL in 15 min using laboratory and clinical isolates of DENV. No cross-reaction between DENV serotypes was observed in these DENV isolates. We also confirmed that there was no cross-reaction with chikungunya, Japanese encephalitis, Sindbis, and Zika viruses. Evaluation of these systems using serum from DENV-infected individuals indicated a serotype specificity of almost 100%. These assay systems could accelerate both DENV infection diagnosis and epidemiologic studies in DENV-endemic areas.

Acalculous Cholecystitis in a Young Adult with Scrub Typhus: A Case Report and Epidemiology of Scrub Typhus in the Maldives.

Scrub typhus is a neglected tropical disease predominantly occurring in Asia. The causative agent is a bacterium transmitted by the larval stage of mites found in rural vegetation in endemic regions. Cases of scrub typhus frequently present as acute undifferentiated febrile illness, and without early diagnosis and treatment, the disease can develop fatal complications. We retrospectively reviewed de-identified data from a 23-year-old woman who presented to an emergency department with complaints of worsening abdominal pain. On presentation, she appeared jaundiced and toxic-looking. Other positive findings on abdominal examination were a positive Murphey's sign, abdominal guarding and hepatosplenomegaly. Magnetic resonance cholangiopancreatography demonstrated acalculous cholecystitis. Additional findings included eschar on the medial aspect of the left thigh with inguinal regional lymphadenopathy. Further, positive results were obtained for immunoglobulins M and G, confirming scrub typhus. The workup for other infectious causes of acute acalculous cholecystitis (AAC) detected antibodies against human herpesvirus 4 (Epstein-Barr virus), suggesting an alternative cause of AAC. Whether that represented re-activation of the Epstein-Barr virus could not be determined. As other reports have described acute acalculous cholecystitis in adult scrub typhus patients, we recommend doxycycline to treat acute acalculous cholecystitis in endemic regions while awaiting serological confirmation.

Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 Infection in an Adult: A Case Report from the Maldives.

The multisystem inflammatory syndrome in adults (MIS-A) is a novel syndrome observed during COVID-19 outbreaks. This hyper-inflammatory syndrome is seen predominantly in children and adolescents. The case of an adult from the Maldives who had asymptomatic SARS-CoV-2 infection three weeks before presenting to the hospital with fever, rash, and shock is presented. De-identified clinical data were retrospectively collected to summarize the clinical progression and treatment during hospitalization and the six-month follow-up. SARS-CoV-2 infection was confirmed by RT-PCR. Other laboratory findings included anemia (hemoglobin: 9.8 g/dL), leukocytosis (leukocytes: 20,900/µL), neutrophilia (neutrophils: 18,580/µL) and lymphopenia (lymphocytes: 5067/µL), and elevated inflammatory markers, including C-reactive protein (34.8 mg/dL) and ferritin (2716.0 ng/dL). The electrocardiogram had low-voltage complexes, and the echocardiogram showed hypokinesia, ventricular dysfunction, and a pericardial effusion suggestive of myocardial dysfunction compromising hemodynamics and causing circulatory shock. These findings fulfilled the diagnostic criteria of MIS-A. The case was managed in the intensive care unit and required non-invasive positive pressure ventilation, inotropes, and steroids. With the new surges of COVID-19 cases, more cases of MIS-A that require the management of organ failure and long-term follow-up to recovery are anticipated. Clinicians should therefore be vigilant in identifying cases of MIS-A during the pandemic.

Clinical Features of Acute Chikungunya Virus Infection in Children and Adults during an Outbreak in the Maldives.

The chikungunya virus is an arthritogenic arbovirus that has re-emerged in many tropical and subtropical regions, causing explosive outbreaks. This re-emergence is due to a genomic polymorphism that has increased the vector susceptibility of the virus. The majority of those infected with chikungunya virus exhibit symptoms of fever, rash, and debilitating polyarthralgia or arthritis. Symptoms can persist for weeks, and patients can relapse months later. Fatalities are rare, but individuals of extreme age can develop severe infection. Here, we describe the 2019 outbreak, the second-largest since the virus re-emerged in the Maldives after the 2004 Indian Ocean epidemic, in which a total of 1,470 cases were reported to the Health Ministry. Sixty-seven patients presenting at the main referral tertiary care hospital in the Maldives capital with acute undifferentiated illness were recruited following a negative dengue serology. A novel point-of-care antigen kit was used to screen suspected cases, 50 of which were subsequently confirmed using real-time reverse transcription-polymerase chain reaction. We describe the genotype and polymorphism of Maldives chikungunya virus using phylogenetic analysis. All isolates were consistent with the East Central South African genotype of the Indian Ocean lineage, with a specific E1-K211E mutation. In addition, we explored the clinical and laboratory manifestations of acute chikungunya in children and adults, of which severe infection was found in some children, whereas arthritis primarily occurred in adults. Arthritides in adults occurred irrespective of underlying comorbidities and were associated with the degree of viremia.

A Cluster of Dengue Cases in Travelers: A Clinical Series from Thailand.

Dengue is an overlooked tropical disease for which billions of people are at risk. The disease, caused by a Flavivirus with four distinct serotypes, is transmitted primarily by urban Aedes mosquito species. The infection leads to a spectrum of clinical manifestations, with the majority being asymptomatic. Primary dengue fever and, to a greater extent, a subsequent infection with a different serotype is associated with increased severity. Increased global travel and recreational tourism expose individuals naïve to the dengue viruses, the most common arboviral infections among travelers. We describe a cluster of possible primary acute dengue infections in a group of 12 individuals who presented to Bangkok Hospital for Tropical Diseases in 2017. Infection was confirmed by dengue NS1 antigen and multiplex real-time RT-PCR. Nine individuals required hospitalization, and four developed dengue warning signs. Leukocytes, neutrophils, and platelets declined towards defervescence and were negatively correlated with day of illness. Six clinical isolates were identified as dengue serotype-1, with 100% nucleotide identity suggesting that these patients were infected with the same virus.

Antibody-dependent enhancement representing in vitro infective progeny virus titer correlates with the viremia level in dengue patients.

Dengue virus (DENV) causes dengue fever (DF) and dengue hemorrhagic fever in humans. Some DF patients suddenly develop severe symptoms around the defervescent period. Although the pathogenic mechanism of the severe symptoms has not been fully elucidated, the viremia level in the early phase has been shown to correlate with the disease severity. One of the hypotheses is that a phenomenon called antibody-dependent enhancement (ADE) of infection leads to high level of viremia. To examine the plausibility of this hypothesis, we examined the relationship between in vitro ADE activity and in vivo viral load quantity in six patients with dengue diseases. Blood samples were collected at multiple time points between the acute and defervescent phases, and the balance between neutralizing and enhancing activities against the autologous and prototype viruses was examined. As the antibody levels against DENV were rapidly increased, ADE activity was decreased over time or partially maintained against some viruses at low serum dilution. In addition, positive correlations were observed between ADE activity representing in vitro progeny virus production and viremia levels in patient plasma samples. The measurement of ADE activity in dengue-seropositive samples may help to predict the level of viral load in the subsequent DENV infection.

Post-Chikungunya Virus Infection Musculoskeletal Disorders: Syndromic Sequelae after an Outbreak.

The Chikungunya virus is a re-emerging mosquito-borne alphavirus. Outbreaks are unpredictable and explosive in nature. Fever, arthralgia, and rash are common symptoms during the acute phase. Diagnostic tests are required to differentiate chikungunya virus from other co-circulating arboviruses, as symptoms can overlap, causing a dilemma for clinicians. Arthritis is observed during the sub-acute and chronic phases, which can flare up, resulting in increased morbidity that adversely affects the activities of daily living. During the 2019 chikungunya epidemic in Thailand, cases surged in Bangkok in the last quarter of the year. Here, we demonstrate the chronic sequelae of post-chikungunya arthritis in one of our patients one year after the initial infection. An inflammatory process involving edema, erythema, and tenderness to palpation of her fingers' flexor surfaces was observed, with positive chikungunya IgG and negative IgM tests and antigen. The condition produced stiffness in the patient's fingers and limited their range of motion, adversely affecting daily living activities. Resolution of symptoms was observed with a short course of an anti-inflammatory agent. More research is required to determine whether sanctuaries enable chikungunya virus to evade the host immune response and remain latent, flaring up months later and triggering an inflammatory response that causes post-chikungunya arthritis.

Coronavirus disease 2019 and dengue: two case reports.

BACKGROUND: The pandemic of this century has overwhelmed the healthcare systems of affected countries, and all resources have been diverted to coronavirus disease 2019. At the onset, coronavirus disease 2019 can present as any other acute febrile undifferentiated illness. In tropical regions, clinicians are increasingly challenged to differentiate these febrile illnesses without the use of diagnostics. With this pandemic, many of these tropical diseases are neglected and go underreported. Dengue is holoendemic in the Maldives, and dengue viruses circulate throughout the year. Reports about coinfections with dengue virus and severe acute respiratory syndrome coronavirus 2 are scarce, and the outcome and the dynamics of the disease may be altered in the presence of coinfection. We have described the clinical manifestation and serial laboratory profile, and highlighted the atypical findings uncommon in dengue infection. CASE PRESENTATION: Case 1 was a 39-year old Asian male, presented on day 6 of dengue infection with warning signs. Reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 that was done as per hospital protocol was found to be positive. Case 2 was a 38-year old Asian male, was admitted on day 5 of illness with symptoms of acute respiratory infection with positive reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2. Evaluation of progressive leukopenia and thrombocytopenia showed positive dengue serology. CONCLUSION: Clinicians must be conscientious when working on the differential diagnosis of possible tropical diseases in cases of coronavirus disease 2019, specifically, when patients develop hemoconcentration, thrombocytopenia, and transaminitis with elevated expression of aspartate higher than alanine transaminase, which is frequently observed in dengue infection. Caution must be taken during the administration of intravenous fluids when treating patients with coronavirus disease 2019 and dengue coinfection, as coronavirus disease 2019 patients are more prone to develop pulmonary edema. Timely diagnosis and appropriate management are essential to avoid the devastating complications of severe forms of dengue infection. It is important to repeat and reconfirm the dengue serology in coronavirus disease 2019 patients to avoid false positivity. Diligence and care must be taken not to neglect other endemic tropical diseases in the region during the present pandemic.

COVID-19 and emergencies in patients with diabetes: two case reports.

BACKGROUND: Maldives reported its first Coronavirus disease 2019 (COVID-19) case on March 7th, 2020. Since then more than 9400 positive cases and 33 deaths have been reported. Recently studies have shown that COVID-19 patients with diabetes had a poor prognosis and a higher mortality rate when compared to the non-diabetic patients. Poorly controlled diabetic patients had a higher incidence of complications like diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) which might have been precipitated by COVID-19. DKA and HHS are potentially lethal but preventable conditions. During this pandemic, although cases of uncontrolled diabetes are frequently reported, there is scarcity in reporting of cases with diabetic emergencies. CASE PRESENTATION: Case 1 was a 53-year old Asian male, admitted on Day 10th of illness with DKA with acute kidney injury, and Moderate COVID-19. Case 2 was a 72-year old Asian male, admitted with mild COVID-19 who developed HHS with acute kidney injury on day 9 of illness. Both patients were managed conservatively in intensive care unit, with intravenous fluids and insulin. CONCLUSION: Clinicians should focus on close monitoring of diabetic patients with COVID-19, to prevent diabetic emergencies like DKA and HHS. It is important to aggressively manage these conditions for a favorable outcome.