The American Journal of Tropical Medicine and Hygiene - Current Issue

A 2-visit multiple-site intradermal (ID) vaccine protocol would be the most economical, immunogenic, and practicable regimen for postexposure rabies prophylaxis (PEP) in clinics seeing few patients a month. This regimen with an additional day 28 dose is now recommended by the WHO. The difficulties surrounding ID rabies vaccination have hindered progress in provision of prophylaxis, especially in rural Asia and Africa. Although the latest WHO recommendations include 1-week ID postexposure vaccine regimens, these are unlikely to prove economical where rabies vaccination is presently unavailable. The new protocol uses a whole vial of vaccine divided between 4-sites ID on the first day and half a vial at 2-sites ID on day 7. Gavi has recently approved support for rabies PEP. This 2-visit 4-site ID regimen, with or without a day 28 dose, should be considered for implementation in this remarkable new initiative.

In this review, we provide an epidemiological history of the emergence and ongoing spread of evolving Plasmodium falciparum artemisinin resistance (ARTR). Southeast Asia has been the focal point for emergence and spread of multiple antimalarial drug resistance phenomena, and is once again for evolving ARTR, also known as the “delayed clearance phenotype” (DCP). The five countries most impacted, Cambodia, Thailand, Myanmar, Laos, and Vietnam, each have complex histories of antimalarial drug use over many decades, which have in part molded the use of various artemisinin combination therapies (ACTs) within each country. We catalog the use of ACTs, evolving loss of ACT efficacy, and the frequency of pfk13 mutations (mutations associated with ARTR) in the Greater Mekong Subregion and map the historical spread of ARTR/DCP parasites. These data should assist improved surveillance and deployment of next-generation ACTs.

Alphaviruses (Togaviridae, Alphavirus) are arthropod-borne single-stranded RNA pathogens that cause febrile and neurologic disease in much of Latin America. However, many features of Alphavirus epidemiology remain unknown. In 2011, we undertook a cross-sectional study in Nueva Esperanza, an indigenous community in the Peruvian Amazon. Here, we present the first serologic evidence of Mayaro (MAYV), Venezuelan equine encephalitis (VEE) complex alphavirus, Una (UNAV), and Madariaga (MADV) viruses reported in humans (24%, 16%, 13%, and 1.5%, respectively) from an Amazonian indigenous community in Peru. Hunting activity and cohabiting with hunters were the main risk factors for Mayaro seroconversion, but only hunting was associated with UNAV seropositivity. Our results suggest that alphavirus infection in this region is common, but we highlight the high UNAV seroprevalence found and corroborate the low MADV prevalence reported in this region. Furthermore, MAYV-neutralizing antibodies were also detected in stored samples from wild animals (18%) hunted by Nueva Esperanza inhabitants and another mestizo community located close to Iquitos. Further serological surveys of VEE complex alphaviruses, UNAV, and MADV in wild animals and assessing the ability of the MAYV seropositive species to transmit the virus will be relevant.

Fifty-two febrile patients living in Barquisimeto, Venezuela, were screened for arbovirus infection by virus culture during an outbreak of what was thought to be Zika virus infection. We report identification of Mayaro virus (MAYV) on culture of plasma from one patient, an 18-year-old woman with acute febrile illness, arthralgias, and psoriasiform rash. The strain was sequenced and was found to be most closely related to a 1999 strain from French Guiana, which, in turn, was related to two 2014 strains from Haiti. By contrast, previously reported outbreak-related MAYV strains from a sylvatic area approximately 80 miles from where the case patient lived were most closely related to Peruvian isolates. The two strain groups show evidence of having diverged genetically approximately 100 years ago.

Dengue fever is the most prevalent arbovirus infection among humans, and tropical regions are hyperendemic for this infection. The number of solid organ transplant recipients is continuously increasing, and there are few data regarding the clinical course and outcomes of dengue infection among this population. We report on a retrospective case series of solid organ transplant recipients with dengue virus infection from 2001 to 2018 at Fundación Valle del Lili in Cali, Colombia. A total of 20 patients were included. The median age was 50.5 years (interquartile range [IQR] = 31–63.5 years) and 65% were female. Regarding the clinical course, 75% of patients had at least one warning sign, 45% were managed in the intensive care unit, and 30% had severe dengue. The median of time from transplant and dengue infection was 27.6 months (IQR = 3.82–59.12 months), and three patients had the disease in the first month after the transplant. All patients were discharged, and none of them had graft rejection. Dengue is an endemic disease in our region and represents a threat among solid organ transplantation recipients. All patients had a full recovery after the infection, suggesting that timely and effective management of patients and the access to high-complexity services could prevent fatal cases.

Influenza A and B outbreaks occur each year with different activity and molecular patterns. To date, knowledge of seasonal epidemiology remains a prerequisite not only to put in place the most effective immunization strategy against influenza but also to identify population groups at higher risk of developing serious complications. A retrospective analysis of influenza surveillance data from 2010 to 2018 aimed to explore the epidemiology of influenza in Sicily, at the primary care and hospital level. Overall, 6,740 patients with acute respiratory infection were tested, of which 3,032 (45.0%) were positive for influenza. The relative proportion of type A and B viruses markedly varied across seasons. Type A similarly spreads among children and adults, whereas type B was more commonly identified among pediatric population aged 5–9 years. The median age of confirmed influenza cases differed by health-care setting, increasing according to disease severity (range: 8–54 years). Among influenza-confirmed cases, more than 80% of hospitalized patients had an underlying medical condition. Cardiovascular disease, lung disease, diabetes, and obesity were some of the most frequent. Overall, patients admitted to an intensive care unit were more likely to have multiple comorbidities and being infected with influenza infection strongly increased the risk of severe clinical outcomes. Understanding of the epidemiology of influenza and the molecular features of circulating viruses is of paramount importance to optimize prevention and control strategies. Knowledge of predictors for the occurrence of severe forms of the disease may help to address adequate preventive measures to high-risk population groups.

Poliovirus (PV) environmental surveillance was established in Haiti in three sites each in Port-au-Prince and Gonaïves, where sewage and fecal-influenced environmental open water channel samples were collected monthly from March 2016 to February 2017. The primary objective was to monitor for the emergence of vaccine-derived polioviruses (VDPVs) and the importation and transmission of wild polioviruses (WPVs). A secondary objective was to compare two environmental sample processing methods, the gold standard two-phase separation method and a filter method (bag-mediated filtration system [BMFS]). In addition, non-polio enteroviruses (NPEVs) were characterized by next-generation sequencing using Illumina MiSeq to provide insight on surrogates for PVs. No WPVs or VDPVs were detected at any site with either concentration method. Sabin (vaccine) strain PV type 2 and Sabin strain PV type 1 were found in Port-au-Prince, in March and April samples, respectively. Non-polio enteroviruses were isolated in 75–100% and 0–58% of samples, by either processing method during the reporting period in Port-au-Prince and Gonaïves, respectively. Further analysis of 24 paired Port-au-Prince samples confirmed the detection of a human NPEV and echovirus types E-3, E-6, E-7, E-11, E-19, E-20, and E-29. The comparison of the BMFS filtration method to the two-phase separation method found no significant difference in sensitivity between the two methods (mid-P-value = 0.55). The experience of one calendar year of sampling has informed the appropriateness of the initially chosen sampling sites, importance of an adequate PV surrogate, and robustness of two processing methods.

Human granulocytic anaplasmosis (HGA), caused by the bacteria Anaplasma phagocytophilum, is transmitted to humans by blacklegged ticks (Ixodes scapularis) in eastern North America. To assess the emergence of A. phagocytophilum in Ontario, we analyzed patient serological and clinical data in combination with pathogen detection in blacklegged ticks from 2011 to 2017. Our sample population included all patients who had Anaplasma serological testing ordered by their physicians (n = 851). Eighty-three patients (10.8%) were A. phagocytophilum seropositive (IgG titers ≥ 1:64) and 686 (89.2%) were seronegative (IgG titers < 1:64). Applying published surveillance case definitions, we classified zero as confirmed, five as probable, and 78 as suspected cases. The percentage of seropositive patients remained generally stable at 13.6%. Seropositive patients were most often adult females, 40–59 years of age, and reported nonspecific signs and symptoms, such as fatigue, headache, and fever. Higher seropositivity rates (≥ 1.5 patients per 100,000 population) occurred in eastern and northwestern Ontario. The percentage of A. phagocytophilum-positive blacklegged ticks, through passive and active surveillance, was 0.4 and 1.1%, respectively, and increased over time. Serological and entomological indicators of A. phagocytophilum activity increased in areas of the province with established blacklegged tick populations. The risk of HGA is presently low in Ontario; however, further research is required to document the epidemiology of HGA in the province. To minimize the impact of HGA emergence in Ontario, increased awareness and education of the public and health-care providers is recommended, with consideration to making HGA a reportable infection in Ontario.

Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are the most common tick-borne diseases in South Korea. However, few studies have systematically examined the simultaneous presence of the two diseases. We found that two (4.9%) of 41 patients with suspected and confirmed SFTS had evidence of coinfection with scrub typhus. In addition, two (3.6%) of 55 suspected and confirmed scrub typhus patients were identified to have coinfection with SFTS. Our data suggest that diagnostic evaluation for coinfection in patients with tick-borne illness and empirical doxycycline treatment in patients with SFTS may be warranted in areas endemic for both diseases until coinfection with scrub typhus is ruled out.

In July 2018, acute Q fever (AQF) was diagnosed in two Japanese individuals from the same family. They returned to Japan from Malawi, where the epidemiology of AQF is unknown. A child presented to the hospital with high-grade fever without any symptoms, and a mother presented with fever and dry cough. Paired serum antiphase Ⅱ IgM and IgG significantly elevated in the convalescent phase in both cases. Coxiella burnetii gene (IS1111) was detected from the mother’s blood sample. They had no reported direct animal contact, but the onset of symptoms coincided with the dry season in Malawi, which may have facilitated environmental dispersal. These cases may serve as an alert for high-risk people to possible AQF spread and underdiagnosis in Malawi.

Leptospirosis is a zoonotic bacterial disease caused by pathogenic species of the genus Leptospira. Disease incidence is known to be attributed to environmental and social conditions which promote the spread of reservoir hosts, primarily rodents. A well-being program was conducted to determine the seroprevalence and risk factors associated with leptospirosis in urban poor communities occupying low-cost flat accommodation and squatter settlements in the vicinity of Wilayah Persekutuan, Kuala Lumpur. Blood samples from a total of 532 volunteers were screened for the detection of IgG and IgM antibodies against leptospirosis using ELISA. Demographic data were collected for each participant through a questionnaire survey before blood collection. The overall seroprevalence was low (12.6%, n = 67/532; 95% CI: 9.9–15.7%), with 8.1% (n = 43/532) being seropositive for anti-Leptospira IgG, indicating previous infection, and 4.9% (n = 26/532) for anti-Leptospira IgM, indicating current infection. Two significant factors such as host age (P ≤ 0.01) and knowledge of disease transmission (P = 0.017) significantly influenced the presence of anti-Leptospira IgM, whereas the detection of anti-IgG indicated the presence of clean drinking water sources (P = 0.043). Despite the low prevalence, the transmission of leptospirosis does occur among urban poor communities, suggesting the need for undertaking public awareness programs.

African multimammate rats, Mastomys natalensis, are widely distributed in sub-Saharan Africa and live in close association with humans. In West Africa, numerous field studies have shown these animals may be naturally infected with the relapsing fever spirochete Borrelia crocidurae, the primary cause of tick-borne relapsing fever in this region of the continent. However, naturally infected individual rats have never been examined over time; therefore, the true host competency of these rats for this spirochete is unknown. Therefore, using animals from an established laboratory colony of M. natalensis, rats were experimentally infected with B. crocidurae and their blood examined to 28 days postinoculation. These animals were highly susceptible to infection and displayed prolonged and cyclic spirochetemias. Our results demonstrate these peridomestic rodents are likely competent hosts for infecting argasid tick vectors and play a primary role in the enzootic cycle for B. crocidurae in West Africa.

In the present study, we tested 391 fleas collected from guinea pigs (Cavia porcellus) (241 Pulex species, 110 Ctenocephalides felis, and 40 Tiamastus cavicola) and 194 fleas collected from human bedding and clothing (142 Pulex species, 43 C. felis, five T. cavicola, and four Ctenocephalides canis) for the presence of Bartonella DNA. We also tested 83 blood spots collected on Flinders Technology Associates (FTA) cards from guinea pigs inhabiting 338 Peruvian households. Bartonella DNA was detected in 81 (20.7%) of 391 guinea pig fleas, in five (2.6%) of 194 human fleas, and in 16 (19.3%) of 83 guinea pig blood spots. Among identified Bartonella species, B. rochalimae was the most prevalent in fleas (89.5%) and the only species found in the blood spots from guinea pigs. Other Bartonella species detected in fleas included B. henselae (3.5%), B. clarridgeiae (2.3%), and an undescribed Bartonella species (4.7%). Our results demonstrated a high prevalence of zoonotic B. rochalimae in households in rural areas where the research was conducted and suggested a potential role of guinea pigs as a reservoir of this bacterium.

Infection caused by invasive Salmonella occurs when Salmonella bacteria, which normally cause diarrhea, enter the bloodstream and spread through the body. We report the dramatic increase in florfenicol-resistant invasive non-typhoidal Salmonella (iNTS) in China between 2007 and 2016. Of the 186 iNTS strains isolated during the study period, 34 were florfenicol resistant, most of which harbored known resistance genes. Florfenicol is exclusively used in veterinary medicine in China, but now florfenicol-resistant iNTS is found in clinical patients. This finding indicates that antimicrobial resistance produced in veterinary medicine can be transmitted to humans, which poses a severe threat to public health.