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The American Journal of Tropical Medicine and Hygiene - Online First
In order to provide our readers with timely access to new content, papers accepted by the American Journal of Tropical Medicine and Hygiene are posted online ahead of print publication. Papers that have been accepted for publication are peer-reviewed and copy edited but do not incorporate all corrections or constitute the final versions that will appear in the Journal. Final, corrected papers will be published online concurrent with the release of the print issue.
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A Pilot Study to Assess Safety and Feasibility of Intrathecal Immunoglobulin for the Treatment of Adults with Tetanus
Authors: Huynh Thi Loan, Lam Minh Yen, Evelyne Kestelyn, Nguyen Van Hao, Nguyen Thi Hoang Mai, Duong Bich Thuy, Ha Thi Hai Duong, Nguyen Thi Phuong Dung, Nguyen Hoan Phu, Pham Thi Lieu, Tran Tan Thanh, Ronald Geskus, H. Rogier van Doorn, Le Van Tan, Duncan Wyncoll, Nicholas P. J. Day, Tran Tinh Hien, Guy E. Thwaites, Nguyen Van Vinh Chau and C. Louise ThwaitesAvailable online: 18 June 2018More LessTetanus remains a significant burden in many low- and middle-income countries. The tetanus toxin acts within the central nervous system and intrathecal antitoxin administration may be beneficial, but there are safety concerns, especially in resource-limited settings. We performed a pilot study to assess the safety and feasibility of intrathecal human tetanus immunoglobulin in five adults with tetanus before the conduct of a large randomized controlled trial. Intrathecal injection via lumbar puncture was given to all patients within a median 140 (range 100–165) minutes of intensive care unit (ICU) admission. There were no serious adverse effects associated with the procedure although three patients had probably related minor adverse events which resolved spontaneously. Median ICU length of stay was 14 (range 5–17) days. Two patients required mechanical ventilation and one developed a deep vein thrombosis. Within 240 days of hospital discharge, no patients died and all patients returned to work.
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Acceptability and Feasibility of Sharing a Soapy Water System for Handwashing in a Low-Income Urban Community in Dhaka, Bangladesh: A Qualitative Study
Available online: 11 June 2018More LessHandwashing with soap at key times is an effective means of reducing pathogen transmission. In a low-income community in urban Dhaka, we piloted and evaluated the acceptability and feasibility of a shared handwashing intervention. This included promotion by community health promoters of a homemade solution of detergent powder mixed with water and stored in a 1.5-L reclaimed mineral water bottle. Community health promoters encouraged sharing of the recurrent detergent cost among compound members. Of 152 participating compounds, fieldworkers randomly selected 60 for qualitative assessment. Fieldworkers conducted 30 in-depth interviews and five focus group discussions among purposively selected compound members. The reclaimed bottles served as an easily accessible dispenser for the soapy water, which could feasibly be retained next to the toilet and kitchen areas for communal use. Bottles functioned as a positive reminder for handwashing at recommended key times. Most compounds (45/60, 75%) shared a common soapy water system and its associated costs. There was reluctance to prepare soapy water for shared use in the remaining 25%. Soapy water was an acceptable hand cleaning agent, with the bottle as a feasible dispenser. It was simple in design, cost-effective, replicable, popular with intervention recipient, and neighboring nonrecipients, and commonly shared among nonrelated households. The need to share expenses and product preparation served as a barrier. Developing a sustainable maintenance system, therefore, is critical to ensuring the public health benefits of handwashing with soap.
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Toward Point-of-Care Drug Quality Assurance in Developing Countries: Comparison of Liquid Chromatography and Infrared Spectroscopy Quantitation of a Small-Scale Random Sample of Amoxicillin
Authors: Norah Alotaibi, Sean Overton, Sharon Curtis, Jason W. Nickerson, Amir Attaran, Sheldon Gilmer and Paul M. MayerAvailable online: 11 June 2018More LessSubstandard antibiotics are thought to be a major threat to public health in developing countries and a cause of antimicrobial resistance. However, assessing quality outside of a laboratory setting, using simple equipment, is challenging. The aim of this study was to validate the use of a portable Fourier transform infrared (FT-IR) spectrometer for the identification of substandard antibiotics. Results are presented for amoxicillin packages from Haiti, Ghana, Sierra Leone, Democratic Republic of Congo, India, Papua New Guinea, and Ethiopia collected over the course of 6 months in 2017, including two field trips with the FT-IR to Ghana and Sierra Leone. Canadian samples were used as a control. Regarding drug quality, of 290 individual capsules of amoxicillin analyzed, 13 were found to be substandard with total active pharmaceutical ingredients (API) lying outside the acceptable range of 90–110%. Of these 13, four were below 80% API. The FT-IR reliably identified these outliers and was found to yield results in good agreement with the established pharmacopeia liquid chromatography protocol. We conclude that the portable FT-IR may be suitable to intercept substandard antibiotics in developing countries where more sophisticated techniques are not readily available.
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An Evolving Choice in a Diverse Water Market: A Quality Comparison of Sachet Water with Community and Household Water Sources in Ghana
Authors: Danice Guzmán and Justin StolerAvailable online: 11 June 2018More LessPackaged water, particularly bagged sachet water, has become an important drinking water source in West Africa as local governments struggle to provide safe drinking water supplies. In Ghana, sachet water has become an important primary water source in urban centers, and a growing literature has explored various dimensions of this industry, including product quality. There is very little data on sachet water quality outside of large urban centers, where smaller markets often mean less producer competition and less government regulation. This study analyzes the microbiological quality of sachet water alongside samples of other common water sources at point-of-collection (POC) and point-of-use (POU) in 42 rural, peri-urban, and small-town Ghanaian communities using the IDEXX Colilert® 18. Levels of coliform bacteria and Escherichia coli detected in sachet water samples were statistically and significantly lower than levels detected in all other water sources at POU, including public taps and standpipes, and statistically similar or significantly lower at POC. In diverse waterscapes where households regularly patch together their water supply from different sources, sachet water appears to be an evolving alternative for safe drinking water despite many caveats, including higher unit costs and limited opportunities to recycle the plastic packaging.
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Effective Population Size Differences in Calomys musculinus, the Host of Junín Virus: Its Relationship with the Epidemiological History of Argentine Hemorrhagic Fever
Available online: 11 June 2018More LessArgentine hemorrhagic fever (AHF) is a serious endemic disease in Argentina, produced by Junín virus, whose host is the Sigmodontinae rodent Calomys musculinus. Within the endemic area, human incidence and proportion of infected rodents remains high for 5–10 years after the first appearance of the disease (epidemic [E] zone) and then gradually declines to sporadic cases (historic [H] zone). We tested the hypothesis that host populations within the E zone are large and well connected by gene flow, facilitating the transmission and maintenance of the virus, whereas those in the H and nonendemic (NE) zones are small and isolated, with the opposite effect. We estimated parameters affected by levels of gene flow and population size in 14 populations of C. musculinus: population effective size (N e), genetic variability, and mean relatedness. Our hypothesis was not supported: the lowest levels of variability and of N e and the highest genetic relatedness among individuals were found in the H zone. Populations from the NE zone displayed opposite results, whereas those in the E zone showed intermediate values. If we consider that populations are first NE, then E, and finally H, a correlative decrease in N e was observed. Chronically infected females have a low reproductive success. We propose that this would lower N e because each cohort would originate from a fraction of females of the previous generation, and affect other factors such as proportion of individuals that develop acute infection, probability of viral transmission, and evolution of virulence, which would explain, at least partly, the changing incidence of AHF.
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Carotid Taenia solium Oncosphere Infection: A Novel Porcine Neurocysticercosis Model
Available online: 11 June 2018More LessNeurocysticercosis (NCC), the infection of the human central nervous system (CNS) with larval cysts of Taenia solium causes widespread neurological morbidity. Animal models are crucial for studying the pathophysiology and treatment of NCC. Some drawbacks of current NCC models include differences in the pathogenesis of the model and wild-type parasite, low rates of infection efficiency and lack of reproducibility. We describe a novel porcine model that recreates infection in the CNS with high efficiency. Activated oncospheres, either in a high (45,000–50,000) or low (10,000) dose were inoculated in the common carotid artery of 12 pigs by ultrasound-guided catheterization. Following oncosphere injection, either a high (30 mL) or low (1–3 mL) volume of saline flush was also administered. Cyst burden in the CNS was evaluated independently according to oncosphere dose and flush volume. Neurocysticercosis was achieved in 8/12 (66.7%) pigs. Cyst burden in the CNS of pigs was higher in the high versus the low oncosphere dose category (median: 4.5; interquartile ranges [IQR]: 1–8 and median: 1; IQR: 0–4, respectively) and in the high versus the low flush volume category (median 5.5; IQR: 1–8 and median: 1; IQR: 0–2, respectively), although not statistically different. All cysts in the CNS were viable, whereas both viable and degenerated cysts were found in the musculature. Carotid injection of activated oncospheres in pigs is effective in reproducing NCC. Oncosphere entry into the CNS by way of vasculature mimics wild-type infection, and provides a useful alternative for future investigations on the pathogenesis and antiparasitic treatment of NCC.
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Retinal Parameters as Compared with Head Circumference, Height, Weight, and Body Mass Index in Children in Kenya and Bhutan
Available online: 11 June 2018More LessThe retina shares embryological derivation with the brain and may provide a new measurement of overall growth status, especially useful in resource-limited settings. Optical coherence tomography (OCT) provides detailed quantification of retinal structures. We enrolled community-dwelling children ages 3–11 years old in Siaya, Kenya and Thimphu, Bhutan in 2016. We measured head circumference (age < 5 years only), height, and weight, and standardized these by age and gender. Research staff performed OCT (iScan; Optovue, Inc., Fremont, CA), measuring the peripapillary retinal nerve fiber layer (RNFL) and macular ganglion cell complex (GCC) thicknesses. A neuro-ophthalmologist performed quality control for centration, motion artifact, and algorithm-derived quality scores. Generalized estimating equations were used to determine the relationship between anthropometric and retinal measurements. Two hundred and fifty-eight children (139 females, average age 6.4 years) successfully completed at least one retinal scan, totaling 1,048 scans. Nine hundred and twenty-two scans (88.0%) were deemed usable. Fifty-three of the 258 children (20.5%) were able to complete all six scans. Kenyan children had a thinner average GCC (P < 0.001) than Bhutanese children after adjustment for age and gender, but not RNFL (P = 0.70). In models adjusting for age, gender, and study location, none of standardized height, weight, and body mass index (BMI) were statistically significantly associated with RNFL or GCC. We determined that OCT is feasible in some children in resource-limited settings, particularly those > 4 years old, using the iScan device. We found no evidence for GCC or RNFL as a proxy for height-, weight-, or BMI-for-age. The variation in mean GCC thickness in Asian versus African children warrants further investigation.
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Utilization and Clinical Value of Diagnostic Modalities for Tuberculosis in a High HIV Prevalence Setting
Authors: Stephanie Gati, Rhoda Chetty, Douglas Wilson and Jacqueline M. AchkarAvailable online: 11 June 2018More LessHuman immunodeficiency virus (HIV) infection is a major risk factor for the development of active tuberculosis (TB), one of the deadliest infectious diseases globally. The high mortality associated with the disease can be reduced by early diagnosis and prompt antituberculous treatment initiation. Facilities in TB-endemic regions are increasing the use of nucleic acid amplification (e.g., GeneXpert), which provides rapid results but may have suboptimal sensitivity in HIV-associated TB. Our objective was to evaluate the current practices for TB diagnosis at Edendale Hospital, a large regional hospital in KwaZulu-Natal, South Africa—a TB-endemic region with high HIV prevalence. In this cross-sectional study, all adult inpatients newly started on TB treatment at Edendale were identified over a 6-week period. Demographics, clinical information, diagnostic test results, and outcomes were documented. Pulmonary TB (PTB), extrapulmonary TB (EXTB), and PTB + EXTB were defined as disease evidence in the lungs, other organs, or both, respectively. Ninety-four cases were identified, of which 83% were HIV-associated. Only 30% of all TB patients were microbiologically confirmed, consisting of 7/16 (44%) HIV-uninfected and 21/78 (27%) HIV-infected TB patients. Smear microscopy and mycobacterial culture were seldom ordered. Ultrasound was performed in about one-third of suspected EXTB cases and was valuable in identifying abdominal TB. In this clinical setting with a high incidence of HIV-associated TB, TB diagnosis was more commonly based on clinical assessment and imaging results than on mycobacterial gold standard test confirmation.
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Association of Fecal Markers of Environmental Enteric Dysfunction with Zinc and Iron Status among Children at First Two Years of Life in Bangladesh
Available online: 11 June 2018More LessEnvironmental enteric dysfunction (EED) causes gut inflammation and increased intestinal permeability leading to deficiencies in micronutrients such as zinc and iron. Fecal markers such as myeloperoxidase (MPO), neopterin (NEO), and alpha-1-anti-trypsin (AAT) can predict EED. The aim of this study was to examine the association between fecal markers of EED with zinc and iron status among children at first 2 years of life. Malnutrition and Enteric Disease Study Bangladeshi birth cohort data were used to conduct this analysis. Multivariable analyses using generalized estimating equations were performed to test the association between individual fecal markers with zinc or iron status of the children. A total of 265 children were enrolled in the study (male:female = 1:1). Of the 627 stool samples collected (N = 222 children), 535, 511, and 577 were accompanied by zinc, ferritin, and soluble transferrin receptor values, respectively. Median (interquartile range [IQR]) values of AAT, MPO, and NEO were 0.33 (0.18–0.62) mg/g, 3,895.42 (1,563.76–8,432.82) ng/mL, and 890.81 (331.57–2,089.04) nmol/L, respectively. Overall, 60%, 71%, and 97% of samples were above the values considered normal in nontropical settings for AAT, MPO, and NEO, respectively. High AAT levels were significantly associated with low ferritin values after adjusting for age and gender (coefficient = −5.85; 95% confidence interval = −11.23 to −0.47; P value = 0.03). No such association was found between AAT and plasma zinc status. Myeloperoxidase and NEO were not associated with plasma zinc or iron status. The study results imply the importance of enteric protein loss in contributing to reduced ferritin levels at first 2 years of life.
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Schistosoma mansoni Mass Drug Administration Regimens and Their Effect on Morbidity among Schoolchildren over a 5-Year Period—Kenya, 2010–2015
Available online: 11 June 2018More LessSchistosomiasis control programs are designed to reduce morbidity by providing mass drug administration (MDA) of praziquantel to at-risk populations. We compared morbidity markers between two cohorts of Kenyan schoolchildren that initially had high prevalence of Schistosoma mansoni infections. One cohort (N = 416 at year 1) received four rounds of annual MDA in a community-wide treatment (CWT) strategy. The other cohort (N = 386 at year 1) received school-based treatment (SBT) every other year over the 4-year period. We measured infection with S. mansoni and soil-transmitted helminths (STH) as well as subtle morbidity markers at year 1, year 3, and year 5 and compared cohorts with mixed models after controlling for age and gender. At year 5, neither overall S. mansoni prevalence nor the prevalence of high infection–intensity S. mansoni infection was significantly reduced compared with baseline in either the CWT cohort (N = 277 remaining) or the SBT cohort (N = 235 remaining). Nevertheless, by year 5, children in both cohorts demonstrated significant decreases in wasting, ultrasound-detected organomegaly, and STH infection along with significantly improved pediatric quality-of-life scores compared with year 1. Stunting did not change over time, but children who were S. mansoni egg–positive at year 5 had significantly more stunting than children without schistosomiasis. The only significant difference between arms at year 5 was a lower prevalence of STH infections in the CWT group.
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Genetic Characterization of the Patois Serogroup (Genus Orthobunyavirus; Family Peribunyaviridae) and Evidence That Estero Real Virus is a Member of the Genus Orthonairovirus
Available online: 11 June 2018More LessEstero Real virus (ERV) was isolated in 1980 from Ornithodoros tadaridae ticks collected in El Estero Real, Sancti Spiritus, Cuba. Antigenic characterization of the isolate based on serological methods found a relationship with Abras and Zegla viruses and, consequently, the virus was classified taxonomically within the Patois serogroup. Given the fact that genetic characterization of Patois serogroup viruses has not yet been reported and that ERV is the only virus within the Patois serogroup isolated from ticks, we recently conducted nearly complete genome sequencing in an attempt to gain further insight into the genetic relationship of ERV with other Patois serogroup viruses and members of Peribunyaviridae family (Bunyavirales order). With the exception of ERV, our sequencing and phylogenetic studies revealed the close relationship of the Patois serogroup viruses to each other, forming a clear divergent clade from other members of the Orthobunyavirus genus (Peribunyaviridae family). Notably, our analysis also revealed that ERV forms a monophyletic clade that is closely related to species of the Orthonairovirus genus (Nairoviridae family) in all the genome segments. In light of these findings, we believe that the taxonomic classification of ERV should be revised.
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Malaria Elimination: Lessons from El Salvador
Authors: Adam Bennett and Jennifer L. SmithAvailable online: 11 June 2018More Less
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Parallel Decline of Malaria and Rickettsia felis Infections in Senegal
Authors: Oleg Mediannikov, Cedric Abat, Cheikh Sokhna and Didier RaoultAvailable online: 04 June 2018More LessRickettsia felis is a common emerging pathogen in sub-Saharan Africa. Comparing dynamics of morbidities due to malaria and R. felis infections in two Senegalese villages, we found a strong and significant correlation between them. Malaria morbidity is strongly decreasing because of the implementation of long-lasting insecticidal nets, so we hypothesize that the same measure may decrease the R. felis infections.
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Urban Rodent Surveillance, Climatic Association, and Genomic Characterization of Seoul Virus Collected at U.S. Army Garrison, Seoul, Republic of Korea, 2006–2010
Authors: Heung-Chul Kim, Won-Keun Kim, Jin Sun No, Seung-Ho Lee, Se Hun Gu, Sung-Tae Chong, Terry A. Klein and Jin-Won SongAvailable online: 04 June 2018More LessRodent-borne pathogens pose a critical public health threat in urban areas. An epidemiological survey of urban rodents was conducted from 2006 to 2010 at the U.S. Army Garrison (USAG), Seoul, Republic of Korea (ROK), to determine the prevalence of Seoul virus (SEOV), a rodent-borne hantavirus. A total of 1,950 rodents were captured at USAG, Yongsan, near/in 19.4% (234/1,206) of the numbered buildings. Annual mean rodent infestation rates were the highest for food service facilities, e.g., the Dragon Hill Lodge complex (38.0 rodents) and the Hartell House (18.8 rodents). The brown rat, Rattus norvegicus, accounted for 99.4% (1,939/1,950) of all the rodents captured in the urban area, whereas only 0.6% (11/1,950) of the rodents was house mice (Mus musculus). In November 2006, higher numbers of rats captured were likely associated with climatic factors, e.g., rainfall and temperatures as rats sought harborage in and around buildings. Only 4.7% (34/718) rodents assayed for hantaviruses was serologically positive for SEOV. A total of 8.8% (3/34) R. norvegicus were positive for SEOV RNA by RT-PCR, of which two SEOV strains were completely sequenced and characterized. The 3′ and 5′ terminal sequences revealed incomplete complementary genomic configuration. Seoul virus strains Rn10-134 and Rn10-145 formed a monophyletic lineage with the prototype SEOV strain 80-39. Seoul virus Medium segment showed the highest evolutionary rates compared with the Large and Small segments. In conclusion, this report provides significant insights into continued rodent-borne disease surveillance programs that identify hantaviruses for analysis of disease risk assessments and development of mitigation strategies.
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Rickettsial Infections among Cats and Cat Fleas in Riverside County, California
Available online: 04 June 2018More LessPresently, few studies have investigated the role of domestic cats (Felis catus) in the recrudescence of flea-borne rickettsioses in California and the southern United States. In this study, we aimed to investigate the presence of Rickettsia typhi or Rickettisa felis in domestic cats (F. catus) and the fleas (primarily Ctenocephalides felis, the cat flea) associated with these cats in Riverside County, California. Thirty cats and 64 pools of fleas collected from these cats were investigated for rickettsial infections. Three cats and 17 flea pools (from 10 cats) tested positive for rickettsial infections. PCR and DNA sequencing indicated that one of the cats was positive for R. felis infections, whereas two were positive for Candidatus Rickettsia senegalensis infection. In addition, 12 of the flea pools were positive for R. felis, whereas five were positive for Ca. R. senegalensis. By contrast, no cats or their associated fleas tested positive for R. typhi. Finally, eight sera from these cats contained spotted fever group Rickettsia (SFGR) antibodies. The detection of R. felis and SFGR antibodies and the lack of R. typhi and TGR antibodies support R. felis as the main rickettsial species infecting cat fleas. The detection of Ca. R. senegalensis in both fleas and cats also provides additional evidence that cats and their associated fleas are infected with other R. felis–like organisms highlighting the potential risk for human infections with R. felis or R. felis–like organisms.
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A Community-Designed Play-Yard Intervention to Prevent Microbial Ingestion: A Baby Water, Sanitation, and Hygiene Pilot Study in Rural Zambia
Available online: 04 June 2018More LessMalnourished children in low-income contexts usually suffer from environmental enteric dysfunction, which is damage to the intestines caused by chronic exposure to bacterial pathogens from feces hypothesized to contribute to stunting. Many intervention studies are piloting “Baby water, sanitation, and hygiene (WASH)” to help rural farming families reduce infant and young children’s (IYC’s) exposure to human and free-range livestock feces. One proposed Baby WASH intervention is a play-yard, which consists of a baby-proofed structure (i.e., playpen) that caregivers can place IYC into while doing chores around the household yard. This article describes the pilot development and assessment of a community-built Baby WASH play-yard and a plastic play-yard intervention with 21 caregivers of 6- to 24-month-old IYC in rural Zambia. A modified Trials of Improved Practices approach was used to conduct three visits in each household: an introductory visit during which play-yard use was explained, a second visit consisting of a semi-structured interview and a session of behavioral counseling, and a final visit which included a 2-hour observation of play-yard use. The second and final visits also included 24-hour recalls, and all three visits included spot observations of play-yard use. Reports from caregivers suggest that the community-built play-yard protected IYC from ingesting soil and livestock feces. Barriers to intervention use included caregivers’ WASH beliefs and practices, community reactions, and play-yard maintenance. More work is needed to examine the role of women’s time use in their home environment, community reactions to the intervention, and the biological efficacy to reduce microbial ingestion.
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Case Report: Mucosal Leishmaniasis Presenting with Nasal Septum Perforation after Almost Thirty Years
Authors: Jesùs Rojas-Jaimes, Helena L. Frischtak, Jose Arenas and Andres G. LescanoAvailable online: 04 June 2018More LessMucosal leishmaniasis (ML) is associated with progressive tissue destruction and granuloma formation, often after a considerable period of latency from an initial cutaneous infection. We report a case of recurrent epistaxis of 3 years duration and nasopharyngeal obstruction in a woman with treated cutaneous leishmaniasis nearly 30 years before and with no further exposure to Leishmania. Computed tomography revealed nasal septal perforation and histopathology demonstrated chronic inflammation. Microscopy was negative for amastigotes, but molecular testing of nasal mucosa biopsy detected Leishmania (Viannia) braziliensis. The patient underwent 28 days of treatment with IV sodium stibogluconate and her symptoms improved significantly. Sixteen months after treatment, she continues to have episodic epistaxis and detectable parasite load in her nasal lesion. Although ML is known to take years to decades to develop, there are few reported cases in the literature of such a long latency period. This report highlights the importance of considering ML in the differential diagnosis of chronic epistaxis in countries where leishmaniasis is endemic or in immigrants from these countries, even when presentation occurs decades after leaving an endemic region.
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Arboviral Surveillance among Pediatric Patients with Acute Febrile Illness in Houston, Texas
Available online: 04 June 2018More LessWe instituted active surveillance among febrile patients presenting to the largest Houston-area pediatric emergency department to identify acute infections of dengue virus (DENV), West Nile virus (WNV), and chikungunya virus (CHIKV). In 2014, 1,063 children were enrolled, and 1,015 (95%) had blood and/or cerebrospinal fluid specimens available for DENV, WNV, and CHIKV testing. Almost half (49%) reported recent mosquito bites, and 6% (N = 60) reported either recent international travel or contact with an international traveler. None were positive for acute WNV; three had false-positive CHIKV results; and two had evidence of DENV. One DENV-positive case was an acute infection associated with international travel, whereas the other was identified as a potential secondary acute infection, also likely travel-associated. Neither of the DENV-positive cases were clinically recognized, highlighting the need for education and awareness. Health-care professionals should consider the possibility of arboviral disease among children who have traveled to or from endemic areas.
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Prevalence of and Factors Associated with Negative Microscopic Diagnosis of Cutaneous Leishmaniasis in Rural Peru
Available online: 04 June 2018More LessCutaneous leishmaniasis is endemic to South America where diagnosis is most commonly conducted via microscopy. Patients with suspected leishmaniasis were referred for enrollment by the Ministry of Health (MoH) in Lima, Iquitos, Puerto Maldonado, and several rural areas of Peru. A 43-question survey requesting age, gender, occupation, characterization of the lesion(s), history of leishmaniasis, and insect-deterrent behaviors was administered. Polymerase chain reaction (PCR) was conducted on lesion materials at the Naval Medical Research Unit No. 6 in Lima, and the results were compared with those obtained by the MoH using microscopy. Factors associated with negative microscopy and positive PCR results were identified using χ2 test, t-test, and multivariate logistic regression analyses. Negative microscopy with positive PCR occurred in 31% (123/403) of the 403 cases. After adjusting for confounders, binary multivariate logistic regression analyses revealed that negative microscopy with positive PCR was associated with patients who were male (adjusted OR = 1.93 [1.06–3.53], P = 0.032), had previous leishmaniasis (adjusted OR = 2.93 [1.65–5.22], P < 0.0001), had larger lesions (adjusted OR = 1.02 [1.003–1.03], P = 0.016), and/or had a longer duration between lesion appearance and PCR testing (adjusted OR = 1.12 [1.02–1.22], P = 0.017). Future research should focus on further exploration of these underlying variables, discovery of other factors that may be associated with negative microscopy diagnosis, and the development and implementation of improved testing in endemic regions.
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Snakebite: An Exploratory Cost-Effectiveness Analysis of Adjunct Treatment Strategies
Available online: 04 June 2018More LessThe cost-effectiveness of the standard of care for snakebite treatment, antivenom, and supportive care has been established in various settings. In this study, based on data from South Indian private health-care providers, we address an additional question: “For what cost and effectiveness values would adding adjunct-based treatment strategies to the standard of care for venomous snakebites be cost-effective?” We modeled the cost and performance of potential interventions (e.g., pharmacologic or preventive) used adjunctively with antivenom and supportive care for the treatment of snakebite. Because these potential interventions are theoretical, we used a threshold cost-effectiveness approach to explore this forward-looking concept. We examined economic parameters at which these interventions could be cost-effective or even cost saving. A threshold analysis was used to examine the addition of new interventions to the standard of care. Incremental cost-effectiveness ratios were used to compare treatment strategies. One-way, scenario, and probabilistic sensitivity analyses were conducted to analyze parameter uncertainty and define cost and effectiveness thresholds. Our results suggest that even a 3% reduction in severe cases due to an adjunct strategy is likely to reduce the cost of overall treatment and have the greatest impact on cost-effectiveness. In this model, for example, an investment of $10 of intervention that reduces the incidence of severe cases by 3%, even without changing antivenom usage patterns, creates cost savings of $75 per individual. These findings illustrate the striking degree to which an adjunct intervention could improve patient outcomes and be cost-effective or even cost saving.
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Anopheles Salivary Biomarker as a Proxy for Estimating Plasmodium falciparum Malaria Exposure on the Thailand–Myanmar Border
Available online: 04 June 2018More LessTimely identification and treatment of malaria transmission “hot spots” is essential to achieve malaria elimination. Here we investigate the relevance of using an Anopheles salivary biomarker to estimate Plasmodium falciparum malaria exposure risk along the Thailand–Myanmar border to guide malaria control. Between May 2013 and December 2014, > 9,000 blood samples collected in a cluster randomized control trial were screened with serological assays to measure the Ab responses to Anopheles salivary antigen (gSG6-P1) and P. falciparum malaria antigens (CSP, merozoite surface protein 119 [MSP-119]). Plasmodium falciparum infections were monitored through passive and active case detection. Seroprevalence to gSG6-P1, MSP-119, and CSP were 71.8% (95% Confidence interval [CI]: 70.9, 72.7), 68.6% (95% CI: 67.7, 69.5), and 8.6% (95% CI: 8.0, 9.2), respectively. Multivariate analysis showed that individuals with the highest Ab response to gSG6-P1 had six times the odds of being positive to CSP antigens (P < 0.001) and two times the odds of P. falciparum infection compared with low gSG6-P1 responders (P = 0.004). Spatial scan statistics revealed the presence of clusters of gSG6-P1 that partially overlapped P. falciparum infections. The gSG6-P1 salivary biomarker represents a good proxy for estimating P. falciparum malaria risk and could serve to implement hot spot–targeted vector control interventions to achieve malaria elimination.
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Differential Effects of Temperature and Mosquito Genetics Determine Transmissibility of Arboviruses by Aedes aegypti in Argentina
Available online: 04 June 2018More LessAedes aegypti (L.) (Diptera: Culicidae) have a global distribution and are the primary vector of a number of mosquito-borne viruses responsible for epidemics throughout the Americas. As in much of South America, the threat from pathogens including dengue virus (DENV; Flaviviridae, Flavivirus) and chikungunya virus (CHIKV; Togaviridae, Alphavirus) has increased in Argentina in recent years. The complexity of transmission cycles makes predicting the occurrence and intensity of arbovirus outbreaks difficult. To gain a better understanding of the risk of DENV and CHIKV in Argentina and the factors influencing this risk, we evaluated the role of population and temperature in the vector competence and vectorial capacity (VC) of Ae. aegypti from geographically and ecologically distinct locations. Our results demonstrate that intrinsic and extrinsic factors including mosquito population, viral species, and temperature significantly influence both vector competence and overall VC of Ae. aegypti in Argentina, yet also that the magnitude of these influences is highly variable. Specifically, results suggest that CHIKV competence is more dependent on mosquito genetics than is DENV competence, whereas temperature has a greater effect on DENV transmission. In addition, although there is an overall positive correlation between temperature and competence for both viruses, there are exceptions to this for individual virus–population combinations. Together, these data establish large variability in VC for these pathogens among distinct Ae. aegypti populations in Argentina and demonstrate that accurate assessment of arbovirus risk will require nuanced models that fully consider the complexity of interactions between virus, temperature, mosquito genetics, and hosts.
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Powassan Virus and Other Arthropod-Borne Viruses in Wildlife and Ticks in Ontario, Canada
Available online: 04 June 2018More LessPowassan virus (POWV) is a tick-borne zoonosis maintained in natural enzootic cycles between ixodid ticks and wild mammals. Reported human cases have increased in recent years; these infections can be fatal or lead to long-term neurologic sequelae. However, both the geographic distribution and the role of common, potential mammalian hosts in POWV transmission are poorly understood, creating challenges to public health surveillance. We looked for evidence of POWV infection among candidate wildlife host species and ticks collected from mammals and birds in southern Ontario. Tissues (including blood) and ticks from trapped wild mammals were collected in the summers of 2015 and 2016. Ticks removed from dogs in 2015–2016 and wildlife diagnostic cases from 2011 to 2013 were also included. Tissue and tick (Ixodes spp.) homogenates were tested for POWV by reverse transcriptase–polymerase chain reaction (RT-PCR). In addition, sera from wild mammals were tested for antibodies to POWV, West Nile virus (WNV), and heartland virus (HRTV) by plaque reduction neutralization test. All 724 tissue samples were negative for POWV by RT-PCR. One of 53 pools of Ixodes cookei (among 98 total tick pools) was RT-PCR positive for deer tick virus (POWV) lineage. Antibodies to POWV and WNV were detected in 0.4% of 265 and 6.1% of 264 samples, respectively, and all of 219 serum samples tested negative for anti-HRTV antibodies. These results reveal low POWV detection rates in southern Ontario, while highlighting the challenges and need for continued efforts into understanding POWV epidemiology and targeted surveillance strategies.
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Serological Evidence of Ebola Virus Infection in Rural Guinea before the 2014 West African Epidemic Outbreak
Available online: 04 June 2018More LessQuestions remain as whether an unnoticed Ebola outbreak has occurred in Guinea before the 2014–2016 epidemic. To address this, we used a highly sensitive and specific Luminex-based assay for Ebola virus (EBOV) antibody detection to screen blood samples collected in the framework of the Demographic Health Survey performed in 2012 in Guinea. One sample (GF069) of 1,483 tested was positive at very high immunoglobulin G titer to Zaire EBOV in Guinée Forestière. Thus, at least 2 years before the 2014 EVD outbreak in Guinea, Zaire EBOV was circulating in rural areas of this country.
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Using Reference Quantitative Polymerase Chain Reaction to Assess the Clinical Performance of the Paracheck-Pf® Rapid Diagnostic Test in a Field Setting in Uganda
Authors: Catherine J. Mitran, Anthony K. Mbonye, Michael Hawkes and Stephanie K. YanowAvailable online: 04 June 2018More LessMalaria rapid diagnostic tests (RDTs) are widely used in clinical and surveillance settings. However, the performance of most RDTs has not been characterized at parasite densities below detection by microscopy. We present findings from Uganda, where RDT results from 491 participants with suspected malaria were correlated with quantitative polymerase chain reaction (qPCR)-defined parasitemia. Compared with qPCR, the sensitivity and specificity of the RDT for Plasmodium falciparum mono-infections were 76% (95% confidence interval [CI]: 68–83%) and 95% (95% CI: 92–97%), respectively. The sensitivity of the RDT at parasite densities between 0.2 and 200 parasites/μL was surprisingly high (87%, 95% CI: 74–94%). The high sensitivity of the RDT is likely because of histidine-rich protein 2 from submicroscopic infections, gametocytes, or sequestered parasites. These findings underscore the importance of evaluating different RDTs in field studies against qPCR reference testing to better define the sensitivity and specificity, particularly at low parasite densities.
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Poor Sensitivity of Commercial Rapid Diagnostic Tests for Hepatitis B e Antigen in Senegal, West Africa
Available online: 04 June 2018More LessLimited access to nucleic acid tests for hepatitis B virus (HBV) DNA is a significant barrier to the effective management of chronic HBV infection in resource-poor countries. Alternatively, HBV e antigen (HBeAg) may accurately indicate high viral replication. We assessed the diagnostic performance of three commercially available rapid diagnostic tests (RDTs) for HBeAg (SD Bioline, Insight and OneStep) against a quantitative chemiluminescent immunoassay (CLIA, Architect). Using stored sera from adults with chronic HBV infection, we tested RDTs in three groups in Senegal (48 HBeAg-positive, 196 HBeAg-negative, and 117 cases with high HBV DNA (≥ 106 IU/mL)) and one group in France (17 HBeAg-positive East Asians). In Senegal, the sensitivity and specificity for HBeAg detection were 29.8% and 100% for SD Bioline, 31.1% and 100% for Insight, and 42.5% and 98.4% for OneStep, respectively. The lower limits of detection of these RDTs were very high (> 2.5 log10 Paul Ehrlich Institut units/mL). Their low sensitivity was also confirmed in HBeAg-positive Asian samples (35.3–52.9%). The prevalence of HBeAg in highly viremic (≥ 106 IU/mL) Senegalese patients was low: 58.1% using CLIA and 24.5–37.5% using RDTs. Hepatitis B e antigen prevalence was similarly low in a subgroup of 28 Senegalese women of childbearing age with a high viral load (≥ 106 IU/mL). Approximately, half of highly viremic adults do not carry HBeAg in Africa, and HBeAg RDTs had remarkably poor analytical and diagnostic sensitivity. This implies that HBeAg-based antenatal screening, particularly if using the currently available HBeAg RDTs, may overlook most pregnant women at high risk of mother-to-child transmission in Africa.
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Watch and Wait Approach for Inactive Echinococcal Cyst of the Liver: An Update
Available online: 04 June 2018More LessHuman cystic echinococcosis (CE) is a chronic, complex and neglected infection causing severe disease in humans. Hepatic CE cysts are detected and classified mainly by using ultrasound. Expert opinion and published data suggest that uncomplicated inactive liver cysts do not require treatment and only need to be monitored over time (“Watch and Wait”). Here we update our findings as published in 2014 on the “Watch and Wait” approach applied to inactive, asymptomatic cysts of the liver to keep the medical community informed. Clinical data of patients who accessed the World Health Organization Collaborating Center for CE at the University of Pavia-San Matteo Hospital Foundation from January 1991 to October 2017 were analyzed. Inclusion criteria were presence of one or more inactive uncomplicated cysts in the liver (CE4 or CE5), without any history of previous treatment, and an ultrasound-based follow-up of at least 24 months. Fifty-three patients with 66 inactive cysts fulfilled the inclusion criteria. Of these, 11 patients are newly described here; 37 were part of our previously described cohort and the follow-up for 17 of them was further extended; and five were excluded from the previously published analysis as their follow-up was too short, but could be included now. Without the need for treatment and without development of complications, 98.5% of cysts remained inactive over time. In only one patient (1.9% of patients), a reactivation of one cyst (1.5% of cysts) was observed.
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Dracunculiasis Eradication: Are We There Yet?
Available online: 04 June 2018More LessThis report summarizes the status of the global Dracunculiasis Eradication Program as of the end of 2017. Dracunculiasis (guinea worm disease) has been eliminated from 19 of 21 countries where it was endemic in 1986, when an estimated 3.5 million cases occurred worldwide. Only Chad and Ethiopia reported cases in humans, 15 each, in 2017. Infections of animals, mostly domestic dogs, with Dracunculus medinensis were reported in those two countries and also in Mali. Insecurity and infections in animals are the two main obstacles remaining to interrupting dracunculiasis transmission completely.
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Knowledge, Attitudes, and Preventive Practices Regarding Dengue in Maracay, Venezuela
Available online: 29 May 2018More LessDengue, a viral mosquito-borne disease currently affects more than 2.5 billion people living in endemic areas worldwide. In vector control, social mobilization and community behavioral changes are of crucial importance. Here, we identified the factors influencing community dengue preventive practices in a high-transmission urban area in Venezuela. Between September 2013 and February 2014, a cross-sectional study at the household level was carried out in Maracay city, Venezuela. A precoded questionnaire was used to obtain information on people’s knowledge, attitudes, and use of preventive practices in relation to dengue. Concomitantly, entomological data was collected from households. In 80% of the 105 included households, 1–5 preventive practices (e.g., repellents, insecticides) against mosquito bites were used. However, 57% of the examined houses had potential Aedes breeding sites indoors and/or outdoors, most of which positive for Aedes spp. larvae/pupae. Preventive practices were associated with a previous dengue infection (P = 0.030) and a better knowledge on dengue symptoms and transmission route (P = 0.020). In turn, knowledge was associated with feeling at risk (P < 0.001), a previous dengue infection (P = 0.010), and reported exposure to information sources of dengue (P = 0.011). Even though the knowledge level of the community over transmission ways was high, and most of the individuals took measures to avoid mosquito bites, potential mosquito breeding sites were present in almost two-thirds of the examined properties. Health promotion activities in Venezuela should aim at raising awareness at the community level on the importance of combining mosquito bite prevention with removal of breeding sites in and around the households.
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Occurrence of Chronic Stage Chikungunya in the General Population of Martinique during the First 2014 Epidemic: A Prospective Epidemiological Study
Available online: 29 May 2018More LessChronic stage chikungunya (CHIK), defined by persisting symptoms more than 3 months after initial diagnosis of acute infection, is frequent. However, its burden and impact have rarely been described prospectively in a general population during an ongoing epidemic in the Caribbean. From January 2014 to January 2015, a severe CHIK outbreak occurred in Martinique. Our objective was to describe epidemiological characteristics and outcomes of chronic stage CHIK in its local population. Participants, clinically diagnosed with probable CHIK infection, were included prospectively by general practitioners during the epidemic’s peak from April to October 2014. All identified cases benefited from a follow-up phone call 3 months or more after initial diagnosis during which they were interrogated about persisting clinical signs, past and ongoing treatment, and quality of life. Five hundred and nine subjects participated in the study. Mean age at initial diagnosis was 43.2 ± 23.6 years with a female–male ratio of 1.98. Two hundred participants (39.3%) had probable chronic stage CHIK: 98.5% still experienced pain at least 3 months after acute infection, with 84.3% of reported joint pains; 21.2% were woken up by the pain; 47.2% felt depressed/anxious; and 31.3% experienced memory/concentration disorders. Resumption of daily activity and work was complicated for 55.8% and 36.2% of cases. Persistent impact on morbidity, health outcomes, psychological, and economic aspects further underline the crucial role of community-based medicine and the necessity of an evidence-based multidisciplinary approach toward chronic stage CHIK identification, management, and follow-up in this particular world region.
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Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte–Binding Protein Homologue-5 in Kalifabougou, Mali
Available online: 29 May 2018More LessReticulocyte-binding homologues (RH) are a ligand family that mediates merozoite invasion of erythrocytes in Plasmodium falciparum. Among the five members of this family identified so far, only P. falciparum reticulocyte–binding homologue-5 (PfRH5) has been found to be essential for parasite survival across strains that differ in virulence and route of host-cell invasion. Based on its essential role in invasion and early evidence of sequence conservation, PfRH5 has been prioritized for development as a vaccine candidate. However, little is known about the extent of genetic variability of RH5 in the field and the potential impact of such diversity on clinical outcomes or on vaccine evasion. Samples collected during a prospective cohort study of malaria incidence conducted in Kalifabougou, in southwestern Mali, were used to estimate genetic diversity, measure haplotype prevalence, and assess the within-host dynamics of PfRH5 variants over time and in relation to clinical malaria. A total of 10 nonsynonymous polymorphic sites were identified in the Pfrh5 gene, resulting in 13 haplotypes encoding unique protein variants. Four of these variants have not been previously observed. Plasmodium falciparum reticulocyte–binding homologue-5 had low amino acid haplotype (h = 0.58) and nucleotide (π = 0.00061) diversity. By contrast to other leading blood-stage malaria vaccine candidate antigens, amino acid differences were not associated with changes in the risk of febrile malaria in consecutive infections. Conserved B- and T-cell epitopes were identified. These results support the prioritization of PfRH5 for possible inclusion in a broadly cross-protective vaccine.
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Cervical Lymphatic Filariasis in a Pediatric Patient: Case Report and Database Analysis of Lymphatic Filariasis in the United States
Authors: Jonathan C. Simmonds, Michael K. Mansour and Walid I. DagherAvailable online: 29 May 2018More LessLymphatic filariasis is a mosquito-borne parasitic infection caused by Wuchereria bancrofti and Brugia spp. Commonly seen in tropical developing countries, lymphatic filariasis occurs when adult worms deposit in and obstruct lymphatics. Although not endemic to the United States, a few cases of lymphatic filariasis caused by zoonotic Brugia spp. have been reported. Here we present a case of an 11-year-old female with no travel history who was seen in our clinic for a 1-year history of painless left cervical lymphadenopathy secondary to lymphatic filariasis. We review the literature of this infection and discuss the management of our patient. Using the National Inpatient Sample (NIS), the largest publicly available all-payer inpatient care database in the United States, we also examine the demographics of this infection. Our results show that chronic lymphadenopathy in the head and neck is the most common presenting symptoms of domestic lymphatic filariasis. Diagnosis is often made after surgical lymph node excision. Examination of the NIS from 2000 to 2014 revealed 865 patients admitted with a diagnosis of lymphatic filariasis. Most patients are in the mid to late sixties and are located on the eastern seaboard. Eight hundred and twenty six cases (95.5%) were likely due to zoonotic Brugia spp. and 39 (4.5%) due to W. bancrofti. Despite being rare, these data highlight the need to consider filariasis in patients presenting with chronic lymphadenopathy in the United States.
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Dengue in Singapore from 2004 to 2016: Cyclical Epidemic Patterns Dominated by Serotypes 1 and 2
Available online: 29 May 2018More LessSingapore has experienced periodic dengue epidemics despite maintaining a low Aedes house index. Each epidemic was associated with a switch in the predominant serotype. We investigated the temporal dynamics of dengue fever and dengue virus (DENV) and analyzed the epidemiological and entomological patterns of dengue in Singapore from 2004 to 2016. The case surveillance is based on a mandatory notification system that requires all medical practitioners to report clinically suspected and laboratory-confirmed cases. Circulating (DENV) serotypes are monitored through a virus surveillance program. Entomological surveillance involves inspections for larval breeding and monitoring of adults using gravitraps. Singapore experienced a similar epidemic pattern during 2004–2007 and 2013–2016. The pattern involved a 2-year DENV-1 epidemic occurring after a switch in the predominant serotype from DENV-2 to DENV-1, followed by a “lull” year. Thereafter, the predominant serotype switched back to DENV-2, tailed by a small-scale epidemic. Across the years, the highest incidence group was in the 25–44 years age group. The incidence rate of those aged ≥ 55 years was about half of that of the 15–24 years age group during DENV-1 predominant years. However, it was almost equal to the younger age group in DENV-2 predominant years. Types of Aedes aegypti breeding habitats remained similar. Dengue incidence was significantly higher in areas with high breeding percentage (BP) than areas with low BP (P < 0.05). In conclusion, the oscillation of DENV-1 and DENV-2, throughout the 13-year period, led to a cyclical epidemic pattern and older adults were more affected by DENV-2 than DENV-1.
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Diagnosis of Spotted Fever Group Rickettsioses in U.S. Travelers Returning from Africa, 2007–2016
Available online: 29 May 2018More LessSpotted fever group rickettsioses (SFGRs), such as African tick bite fever (ATBF), are among the most commonly diagnosed diseases for ill travelers returning from southern Africa. We summarized demographic, clinical, and diagnostic features of imported SFGR cases in U.S. travelers returning from Africa who had laboratory specimens submitted to the Centers for Disease Control and Prevention. Diagnosis of SFGR was performed by indirect immunofluorescence antibody assay, immunohistochemical staining, polymerase chain reaction (PCR), or culture. Cases were defined as probable SFGR, confirmed SFGR, or confirmed ATBF. Clinical and epidemiological categorical variables were described as counts and proportions; continuous variables were described using geometric mean titers, median, and range. One hundred and twenty-seven patients satisfied laboratory criteria for confirmed or probable SFGR. Fever was the most common symptom (N = 88; 69%), followed by ≥ 1 eschars (N = 70; 55%). Paired serums were submitted for 36 patients (28%); 12 patients (33%) had nonreactive initial serum sample but converted to a titer ≥ 64 with the convalescent sample. Twenty-seven patients (21%) had infection with Rickettsia africae based on PCR analysis of eschar swab (N = 8) or biopsy (N = 23). Fifteen patients had eschar biopsy or swab samples and serum sample(s) submitted together; 9 (60%) had PCR-positive eschar results and nonreactive acute serology. Health-care providers should consider SFGR when evaluating patients for a febrile illness with eschar and compatible foreign travel history. Polymerase chain reaction testing of eschar biopsies or swabs provides a confirmed diagnosis in early stages of disease; eschar swabs or biopsies are an underutilized diagnostic technique.
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School-Based versus Community-Based Sampling for Trachoma Surveillance
Available online: 29 May 2018More LessTrachoma surveillance is typically performed via random sampling of endemic districts. This strategy minimizes bias and allows examination of preschool children, but is also expensive. Surveillance for some other neglected tropical diseases is carried out in schools, which is logistically easier. In the present study, the prevalence of trachomatous inflammation–follicular (TF) from a population-based sample of children from each of 70 communities in Ethiopia was compared with the corresponding school-based estimate, which was calculated for each community by performing examinations in all primary schools in the district. The overall prevalence of TF was 39.1% (95% confidence interval [CI]: 35.0–43.1%) among children aged 1–9 years in the community-based sample and 18.8% (95% CI: 15.9–21.7%) among children in grades 1–3 of the school-based sample. School-based estimates of TF explained 35% of the variation in the community-based prevalences (P < 0.001). When TF prevalence was used as a diagnostic test for detecting a community with > 5% prevalence of ocular chlamydia, the area under the receiver operating characteristic curve was 0.73 (95% CI: 0.60–0.85) for the school-based sample and 0.71 (0.58–0.83) for the community-based sample (P = 0.76). Thus, although school-based monitoring was necessarily biased relative to population-based monitoring of 1- to 9-year olds, the two methods provided a similar amount of information about the community burden of ocular chlamydia in this trachoma-hyperendemic setting. The generalizability of these findings to areas with less prevalent trachoma is unclear.
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Serologic Evidence of Tick-Borne Encephalitis Virus Infection in a Patient with Suspected Lyme Disease in Japan
Authors: Kentaro Yoshii, Kozue Sato, Mariko Ishizuka, Shintaro Kobayashi, Hiroaki Kariwa and Hiroki KawabataAvailable online: 29 May 2018More LessTick-borne encephalitis (TBE) is widely prevalent on the Eurasian continent, including Japan, but four cases of TBE have been reported in Japan. To inspect unconfirmed TBE cases in Japan, we conducted a retrospective seroepidemiological study of a total of 158 samples from 81 meningoencephalitis patients suspected as Lyme disease. Two serum samples from one patient showed neutralizing antibodies against TBE virus. The patient with severe and progressive encephalitis had a history of tick bite in Hokkaido in 2012. These results demonstrated that tick-borne encephalitis virus (TBEV) case was actually unconfirmed in Japan. Further seroepidemiological surveys are required to identify unconfirmed TBEV infections to consider the pros and cons of introducing specific countermeasures including vaccination in Japan.
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Karyotype Evolution of Chagas Disease Vectors (Hemiptera, Triatominae)
Available online: 21 May 2018More LessThe Triatominae subfamily is composed of 153 hematophagous species that are potential vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Karyotypic studies in triatomines were initiated in 1909. There are 92 karyotypes described, all grouped into the tribes Rhodniini and Triatomini. Recently, a phylogenetic study of the triatomines that combines molecular data with geological changes was performed. We now discuss how the karyotype evolved with the diversification of the triatomines.
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Case Report: Successful Treatment of Chromoblastomycosis Caused by Fonsecaea monophora in a Patient with Psoriasis Using Itraconazole and Acitretin
Authors: Fangfang Bao, Qihua Wang, Changping Yu, Panpan Shang, Lele Sun, Guizhi Zhou, Mei Wu and Furen ZhangAvailable online: 21 May 2018More LessChromoblastomycosis is a worldwide chronic subcutaneous infection caused by dematiaceous fungi and clinically characterized by verrucous lesions. Herein, we report a rare case of chromoblastomycosis caused by Fonsecaea monophora in a 60-year-old male carpenter with a 40-year history of psoriasis from Shandong in northern China. A fungal infection coexisting with psoriasis presents a management dilemma. Our patient responded well to combined itraconazole and acitretin therapy and the lesions resolved completely after 1 month of treatment.
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Cholera Outbreak due to Raw Seafood Consumption in South Korea, 2016
Authors: Jeong Hyun Kim, Jin Lee, Sahyun Hong, Sangwon Lee, Hae-young Na, Young-Il Jeong, Eun Jin Choi, Junyoung Kim, Hyo Sun Kawk and Enhi ChoAvailable online: 21 May 2018More LessThree cases of cholera occurred in South Korea during a period of three weeks in August 2016. All the cases were associated with the consumption of raw seafood in southern coastal area of South Korea. Epidemiologic investigations were performed to track the spread of cholera, including persons in contact with the cholera patients, seafood, and seawater from the fish tank and marine environments. A microbiological investigation demonstrated that cholera isolated from the three patients and a seawater sample at the Korea Strait showed identical serotype (O1 Ogawa), biotype (El tor), and toxin (ctx-positive). Pulsed-field gel electrophoresis analysis showed that the three clinical strains are identical (100%) and shared 97% identity with the seawater sample.
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Preliminary Evidence for the Absence of Cystic Echinococcosis in Gabon: A Cross-Sectional Pilot Survey in Humans and Definitive Hosts
Available online: 21 May 2018More LessCystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval stage of the Echinococcus granulosus sensu lato (s.l.) complex. Although the disease is known to be highly prevalent in certain parts of North and East Africa, data on CE, both in humans and definitive hosts, are extremely scarce for Central Africa. The present study assessed the epidemiology of CE in humans and dogs in rural Gabon. An ultrasound and serologic survey was conducted in volunteers from rural villages in Gabon. A two-step approach was used for serological testing with an indirect hemagglutination assay as a screening test and Western Blot as a confirmatory test. Fecal dog samples were analyzed microscopically, and PCR amplification of nad1 and cox1 genes was performed when taeniid eggs were visible. Regional hospitals and the national reference center for parasitology in Gabon were contacted for information about previous cases of CE. Randomly selected communities were invited to participate. Three hundred and forty-eight human volunteers from these communities were screened. No suspected cases of CE were detected. Definitive host screening was performed from 128 fecal samples from representative subregions, but no eggs from E. granulosus s.l. were found. No documented cases of echinococcosis were reported from the local health-care institutions and the national diagnostic reference center in Gabon. Cystic echinococcosis seems to be very rare or absent in Gabon. The reason for this lack of evidence for echinococcosis is unknown, but the absence of livestock may play a major role.
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Comparison of Two Genotyping Methods for Distinguishing Recrudescence from Reinfection in Antimalarial Drug Efficacy/Effectiveness Trials
Available online: 21 May 2018More LessGenotyping of allelic variants of Plasmodium falciparum merozoite surface proteins 1 and 2 (msp-1 and msp-2), and the glutamate-rich protein is the gold standard for distinguishing reinfections from recrudescences in antimalarial drug trials. We compared performance of the recently developed 24-single-nucleotide polymorphism (SNP) Barcoding Assay against msp-1 and msp-2 genotyping in a cluster-randomized effectiveness trial of artemether–lumefantrine and dihydroartemisinin–piperaquine in Malawi. Rates of recrudescence and reinfection estimated by the two methods did not differ significantly (Fisher’s exact test; P = 0.887 and P = 0.768, respectively). There was a strong agreement between the two methods in predicting treatment outcomes and resolving the genetic complexity of malaria infections in this setting. These results support the use of this SNP assay as an alternative method for correcting antimalarial efficacy/effectiveness data.
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Genetic Variability of Plasmodium vivax in the North Coast of Peru and the Ecuadorian Amazon Basin
Available online: 14 May 2018More LessIn the Peruvian North Coast (PNC), the number of Plasmodium vivax malaria cases increased steadily from 2007 to 2010 despite a significant decline in the overall number of cases in Peru during the same period. To better understand the transmission dynamics of P. vivax populations in the PNC and the neighboring Ecuadorian Amazon Basin (EAB), we studied the genetic variability and population structure of P. vivax in these areas. One hundred and twenty P. vivax isolates (58 from Piura and 37 from Tumbes in the PNC collected from 2008 to 2010 and 25 from the EAB collected in Pastaza from 2001 to 2004) were assessed by five polymorphic microsatellite markers. Genetic variability was determined by expected heterozygosity (He) and population structure by Bayesian inference cluster analysis. We found very low genetic diversity in the PNC (He = 0–0.32) but high genetic diversity in the EAB (He = 0.43–0.70). Population structure analysis revealed three distinct populations in the three locations. Six of 37 (16%) isolates from Tumbes had an identical haplotype to that found in Piura, suggesting unidirectional flow from Piura to Tumbes. In addition, one haplotype from Tumbes showed similarity to a haplotype found in Pastaza, suggesting that this could be an imported case from EAB. These findings strongly suggest a minimal population flow and different levels of genetic variability between these two areas divided by the Andes Mountains. This work presents molecular markers that could be used to increase our understanding of regional malaria transmission dynamics, which has implications for the development of strategies for P. vivax control.
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Factors Associated with the Rapid and Durable Decline in Malaria Incidence in El Salvador, 1980–2017
Authors: Robert A. Burton, José Eduardo Romero Chévez, Mauricio Sauerbrey, Caterina Guinovart, Angela Hartley, Geoffrey Kirkwood, Matthew Boslego, Mirna Elizabeth Gavidia, Jaime Enrique Alemán Escobar, Rachel Turkel, Richard W. Steketee, Laurence Slutsker, Kammerle Schneider and Carlos C. (Kent) CampbellAvailable online: 14 May 2018More LessA decade after the Global Malaria Eradication Program, El Salvador had the highest burden of malaria in Mesoamerica, with approximately 20% due to Plasmodium falciparum. A resurgence of malaria in the 1970s led El Salvador to alter its national malaria control strategy. By 1995, El Salvador recorded its last autochthonous P. falciparum case with fewer than 20 Plasmodium vivax cases annually since 2011. By contrast, its immediate neighbors continue to have the highest incidences of malaria in the region. We reviewed and evaluated the policies and interventions implemented by the Salvadoran National Malaria Program that likely contributed to this progress toward malaria elimination. Decentralization of the malaria program, early regional stratification by risk, and data-driven stratum-specific actions resulted in the timely and targeted allocation of resources for vector control, surveillance, case detection, and treatment. Weekly reporting by health workers and volunteer collaborators—distributed throughout the country by strata and informed via the national surveillance system—enabled local malaria teams to provide rapid, adaptive, and focalized program actions. Sustained investments in surveillance and response have led to a dramatic reduction in local transmission, with most current malaria cases in El Salvador due to importation from neighboring countries. Additional support for systematic elimination efforts in neighboring countries would benefit the region and may be needed for El Salvador to achieve and maintain malaria elimination. El Salvador’s experience provides a relevant case study that can guide the application of similar strategies in other countries committed to malaria elimination.
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Staphylococcus aureus Bacteremia Incidence and Methicillin Resistance in Rural Thailand, 2006–2014
Available online: 14 May 2018More LessStaphylococcus aureus is a common cause of bloodstream infection and methicillin-resistant S. aureus (MRSA) is a growing threat worldwide. We evaluated the incidence rate of S. aureus bacteremia (SAB) and MRSA from population-based surveillance in all hospitals from two Thai provinces. Infections were classified as community-onset (CO) when blood cultures were obtained ≤ 2 days after hospital admission and as hospital-onset (HO) thereafter. The incidence rate of HO-SAB could only be calculated for 2009–2014 when hospitalization denominator data were available. Among 147,524 blood cultures, 919 SAB cases were identified. Community-onset S. aureus bacteremia incidence rate doubled from 4.4 (95% confidence interval [CI]: 3.3–5.8) in 2006 to 9.3 per 100,000 persons per year (95% CI: 7.6–11.2) in 2014. The highest CO-SAB incidence rate was among adults aged 50 years and older. Children less than 5 years old had the next highest incidence rate, with most cases occurring among neonates. During 2009–2014, there were 89 HO-SAB cases at a rate of 0.13 per 1,000 hospitalizations per year (95% CI: 0.10–0.16). Overall, MRSA prevalence among SAB cases was 10% (90/911) and constituted 7% (55/736) of CO-SAB and 20% (22/111) of HO-SAB without a clear temporal trend in incidence rate. In conclusion, CO-SAB incidence rate has increased, whereas MRSA incidence rate remained stable. The increasing CO-SAB incidence rate, especially the burden on older adults and neonates, underscores the importance of strong SAB surveillance to identify and respond to changes in bacteremia trends and antimicrobial resistance.
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Seasonal and Temporal Trends in Childhood Conjunctivitis in Burkina Faso
Available online: 14 May 2018More LessAcute conjunctivitis follows a seasonal pattern. Although its clinical course is typically self-limited, conjunctivitis epidemics incur a substantial economic burden because of missed school and work days. This study investigated seasonal and temporal trends of childhood conjunctivitis in the entire country of Burkina Faso from 2013 to 2016, using routine monthly surveillance from 2,444 government health facilities. A total of 783,314 cases were reported over the 4-year period. Conjunctivitis followed a seasonal pattern throughout the country, with a peak in April. A nationwide conjunctivitis outbreak with a peak in September 2016 was noted (P < 0.001), with an excess number of cases first detected in June 2016. Nationwide passive surveillance was able to detect an epidemic 3 months before its peak, which may aide in allocation of resources for containment and mitigation of transmission in future outbreaks.
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Evaluation of Standard and Mobile Health–Supported Clinical Diagnostic Tools for Assessing Dehydration in Patients with Diarrhea in Rural Bangladesh
Authors: Saadiyah Bilal, Eric Nelson, Lars Meisner, Mahfuj Alam, Saad Al Amin, Yokabed Ashenafi, Shivani Teegala, Md Khan, Nur Alam and Adam LevineAvailable online: 14 May 2018More LessDiarrhea remains a leading cause of morbidity and mortality in patients worldwide. The objective of this study was to determine the relative inter-rater reliability and usability of standard and Mobile health (mHealth)-supported World Health Organization (WHO) algorithms for dehydration assessment in patients with acute diarrhea in a rural, low-income country hospital. Two nurses blinded to each other’s examinations assessed dehydration status on patients soon after hospital arrival using either the standard WHO algorithm printed on a laminated card or an mHealth-supported WHO algorithm downloaded onto a smartphone. The assignment of assessment tool was based on odd or even enrollment date. The inter-rater reliability for dehydration assessment between the two nurses was calculated using Cohen’s K statistic for each study group. A total of 496 patients (< 5 years N = 349, > 5 years N = 147) were enrolled in the study; 132 (27%) had some or severe dehydration, and 364 (73%) had no dehydration on arrival. Cohen’s K statistic demonstrated greater reliability for the mHealth-supported dehydration assessment (0.59) compared with the standard assessment (0.50) in the overall population (P < 0.0001), as well as in the pediatric (0.43 versus 0.37, P < 0.0001) and adult (0.79 versus 0.57, P < 0.0001) populations individually. This is the first study to show that mHealth can improve the reliability of nursing dehydration assessment in patients with acute diarrhea and the first to report on the reliability of the WHO algorithm in adult patients specifically. Future studies should focus on the impact of mHealth-supported dehydration assessment on patient-centered outcomes and examine its reliability in different settings worldwide.
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Evaluation of Argentinean Bird Species as Amplifying Hosts for St. Louis Encephalitis Virus (Flavivirus, Flaviviridae)
Authors: Adrián Díaz, Fernando S. Flores, Agustín I. Quaglia and Marta S. ContigianiAvailable online: 14 May 2018More LessSt.Louis encephalitis virus (SLEV) is an emerging human pathogen flavivirus in Argentina. Recently, it has reemerged in the United States. We evaluated the role as amplifying host of six resident bird species and analyzed their capacity as host during the 2005 encephalitis outbreak of SLEV in Córdoba. Eared dove, picui ground dove, and house sparrow were the three species with highest host competence index. At a city level, eared doves and picui ground doves were the most important amplifying hosts during the 2005 SLEV human outbreak in Córdoba city. This finding highlighted important differences in the SLEV ecology between Argentina and the United States. Characterizing and evaluating the SLEV hosts contribute to our knowledge about its ecology and could help us to understand the causes that promote its emergence as a human pathogen in South America.
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Malaria Elimination: Time to Target All Species
Authors: Andrew A. Lover, J. Kevin Baird, Roly Gosling and Ric PriceAvailable online: 14 May 2018More LessImportant strides have been made within the past decade toward malaria elimination in many regions, and with this progress, the feasibility of eradication is once again under discussion. If the ambitious goal of eradication is to be achieved by 2040, all species of Plasmodium infecting humans will need to be targeted with evidence-based and concerted interventions. In this perspective, the potential barriers to achieving global malaria elimination are discussed with respect to the related diversities in host, parasite, and vector populations. We argue that control strategies need to be reorientated from a sequential attack on each species, dominated by Plasmodium falciparum to one that targets all species in parallel. A set of research themes is proposed to mitigate the potential setbacks on the pathway to a malaria-free world.
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Treatment Delay among Pulmonary Tuberculosis Patients within the Pakistan National Tuberculosis Control Program
Available online: 14 May 2018More LessDelay in diagnosis and treatment worsens the disease and clinical outcomes, which further enhances transmission of tuberculosis (TB) in the community. Therefore, this study aims to assess treatment delay and its associated factors among pulmonary TB patients in Pakistan. A cross-sectional study was conducted among 269 pulmonary TB patients in the district. Binary and multivariate logistic regressions were used to explore the factors associated with delay in TB treatment. Results reveal that most patients were from low socioeconomic backgrounds. For example, 74.7% were living in kacha houses, 54.7% were from lowest the income group (< 250 USD/month), 60.2% married, 54.3% illiterate, 62.5% rural, 56.1% had no house ownership, and 56.5% had insufficient income for daily family expenditures. Significant delays were revealed by this study: 160 patients had experienced a delay of more than 4 weeks, whereas the median delay was 5 weeks. Results show that the most important reason for patient delay was low income and poverty (42.0%) followed by unaware of TB center (41.6), stigma (felt ashamed = 38.7%), and treatment from local traditional healers. Old age (adjusted odds ratio [AOR] = 6.6; 95% confidence interval [CI] = 1.63–26.95); and rural areas patients (AOR = 2.1; 95% CI = 1.15–3.71) were more likely to have experienced delay. However, the higher income and sufficient income category (AOR = 0.5; 95% CI = 0.31–0.95) were associated factors and less likely to experience delay in patient treatment. Integrative prevention interventions, such as those involving community leaders, health extension workers such as lady health workers, and specialized TB centers, would help to reduce delay and expand access to TB-care facilities.
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A Deadly Wait for U.S. Health Insurance Coverage—Sitting on the Couch with Malaria
Authors: Jonathan S. Schultz, Adam J. Atherly and Andrés F. Henao-MartínezAvailable online: 14 May 2018More LessUninsured and unprepared travelers to countries with endemic tropical diseases pose great health-care burdens and financial risks on returning to the United States. We discuss the delayed presentation of an uninsured U.S. traveler returning from West Africa with severe malaria who required intensive care measures to save his life. Despite being critically ill on his return, he sat rigoring on his couch taking antipyretics for 3 days, while he applied for insurance on the Affordable Care Act website and waited for approval because he was fearful of the costs of seeking care. He also had limited access to affordable pretravel consultation and prophylactic medications and did not take them because he had no insurance. Average fees for a malaria hospitalization cost $25,789; however, this patient accumulated fees nearing $300,000—and his care was reimbursed by emergency Medicaid with $39,000, because his newly accepted insurance did not cover his hospitalization. This patients’ experience in the U.S. health-care system with a deadly tropical disease exemplifies the need for affordable universal coverage of pretravel consultation and malaria prophylaxis. In this uncertain political time and the recent removal of the health insurance mandate, along with the White House and Congress wanting to reform health care, this case supports the American Society of Tropical Medicine and Hygiene (ASTMH) statements showing the need for funding of tropical medicine education, research, and public health services for travelers, not cuts to important agencies and insurances that keep our country safe from imported deadly tropical diseases.
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Zika Virus: Knowledge Assessment of Residents and Health-Care Providers in Roatán, Honduras, following an Outbreak
Available online: 14 May 2018More LessFew studies have evaluated the effectiveness of Zika virus (ZIKV) public health educational campaigns. Following a ZIKV educational campaign in Roatán, Honduras (October 2016), a survey was administered (March–May 2017) to residents (N = 348) and health-care professionals ([HCPs]; N = 44) to evaluate ZIKV knowledge, attitudes, and preventive practices, with attention to sexual health. Knowledge scores were calculated and mapped using participants’ home locations. The knowledge scores between HCPs and residents were significantly different (mean 17 versus 11; P < 0.001). Only 6% of residents and 14% of HCPs knew that ZIKV was sexually transmissible. Few reported abstinence (2.6% residents; 9.4% HCPs) or condom use (1.6% residents; 12.5% HCPs) to prevent ZIKV infection. Of all subjects, 15.6% were pregnant or had a pregnant partner in the past year; 57.6% expressed concern over ZIKV. Mapping demonstrated spatial heterogeneity in knowledge. The findings suggest a need for improved public health messaging in ZIKV-affected areas.
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Leptospirosis among Returned Travelers: A GeoSentinel Site Survey and Multicenter Analysis—1997–2016
Authors: Sophia G. de Vries, Benjamin J. Visser, Rhett J. Stoney, Jiri F. P. Wagenaar, Emmanuel Bottieau, Lin H. Chen, Annelies Wilder-Smith, Mary Wilson, Christophe Rapp, Karin Leder, Eric Caumes, Eli Schwartz, Noreen A. Hynes, Abraham Goorhuis, Douglas H. Esposito, Davidson H. Hamer, Martin P. Grobusch and for the GeoSentinel Surveillance NetworkAvailable online: 14 May 2018More LessLeptospirosis is a potentially fatal emerging zoonosis with worldwide distribution and a broad range of clinical presentations and exposure risks. It typically affects vulnerable populations in (sub)tropical countries but is increasingly reported in travelers as well. Diagnostic methods are cumbersome and require further improvement. Here, we describe leptospirosis among travelers presenting to the GeoSentinel Global Surveillance Network. We performed a descriptive analysis of leptospirosis cases reported in GeoSentinel from January 1997 through December 2016. We included 180 travelers with leptospirosis (mostly male; 74%; mostly tourists; 81%). The most frequent region of infection was Southeast Asia (52%); the most common source countries were Thailand (N = 52), Costa Rica (N = 13), Indonesia, and Laos (N = 11 each). Fifty-nine percent were hospitalized; one fatality was reported. We also distributed a supplemental survey to GeoSentinel sites to assess clinical and diagnostic practices. Of 56 GeoSentinel sites, three-quarters responded to the survey. Leptospirosis was reported to have been most frequently considered in febrile travelers with hepatic and renal abnormalities and a history of freshwater exposure. Serology was the most commonly used diagnostic method, although convalescent samples were reported to have been collected infrequently. Within GeoSentinel, leptospirosis was diagnosed mostly among international tourists and caused serious illness. Clinical suspicion and diagnostic workup among surveyed GeoSentinel clinicians were mainly triggered by a classical presentation and exposure history, possibly resulting in underdiagnosis. Suboptimal usage of available diagnostic methods may have resulted in additional missed, or misdiagnosed, cases.
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Arbovirus Surveillance near the Mexico–U.S. Border: Isolation and Sequence Analysis of Chikungunya Virus from Patients with Dengue-like Symptoms in Reynosa, Tamaulipas
Available online: 14 May 2018More LessA total of 1,090 residents of the city of Reynosa, Tamaulipas, on the Mexico–U.S. border presented at hospitals and clinics of the Secretariat of Health, Mexico, in 2015 with symptoms characteristic of dengue. Dengue virus (DENV) antigen was detected by enzyme-linked immunosorbent assay in acute sera from 134 (12.3%) patients. Sera from select patients (N = 34) were also tested for chikungunya virus (CHIKV) RNA by quantitative reverse transcription–polymerase chain reaction. Thirteen (38.2%) patients, including five DENV antigen-positive patients, were positive. Sera from three CHIKV RNA-positive patients were further assayed by virus isolation in cell culture and CHIKV was recovered on each occasion. The genome of one isolate and structural genes of the other two isolates were sequenced. In conclusion, we present evidence of CHIKV and DENV coinfections in patients who live near the Mexico–U.S. border and provide the first genome sequence of a CHIKV isolate from northern Mexico.
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In Southern Nigeria Loa loa Blood Microfilaria Density is Very Low Even in Areas with High Prevalence of Loiasis: Results of a Survey Using the New LoaScope Technology
Available online: 14 May 2018More LessIvermectin treatment can cause central nervous system adverse events (CNS-AEs) in persons with very high-density Loa loa microfilaremia (≥ 30,000 mf/mL blood). Hypoendemic onchocerciasis areas where L. loa is endemic have been excluded from ivermectin mass drug administration programs (MDA) because of the concern for CNS AEs. The rapid assessment procedure for L. loa (RAPLOA) is a questionnaire survey to assess history of eye worm. If ≥ 40% of respondents report eye worm, this correlates with ≥ 2% prevalence of very high-density loiasis microfilaremia, posing an unacceptable risk of CNS-AEs after MDA. In 2016, we conducted a L. loa study in 110 ivermectin-naïve, suspected onchocerciasis hypoendemic villages in southern Nigeria. In previous RAPLOA surveys these villages had prevalences between 10% and 67%. We examined 10,605 residents using the LoaScope, a cell phone–based imaging device for rapidly determining the microfilaria (mf) density of L. loa infections. The mean L. loa village mf prevalence was 6.3% (range 0–29%) and the mean individual mf count among positives was 326 mf/mL. The maximum individual mf count was only 11,429 mf/mL, and among 2,748 persons sampled from the 28 villages with ≥ 40% RAPLOA, the ≥ 2% threshold of very high Loa mf density could be excluded with high statistical confidence (P < 0.01). These findings indicate that ivermectin MDA can be delivered in this area with extremely low risk of L. loa–related CNS-AEs. We also concluded that in Nigeria the RAPLOA survey methodology is not predictive of ≥ 2% prevalence of very high-density L. loa microfilaremia.
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Case Report: Filaria or Megasperm? A Cause of an Ultrasonographic “Filarial Dance Sign”
Authors: J. Brad Wiggers, Hyun-Jung Jang and Jay S. KeystoneAvailable online: 14 May 2018More LessBancroftian filariasis can cause genital abnormalities related to chronic inflammation and obstruction of the afferent lymphatic vessels, and may demonstrate a “filarial dance sign” on scrotal ultrasound with mobile echogenic particles observed. We present a patient with a positive “filarial dance sign,” travel within Latin America and negative filarial serology.
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Comparison of the Pharmacokinetics and Ex Vivo Antimalarial Activities of Artesunate–Amodiaquine and Artemisinin–Piperaquine in Healthy Volunteers for Preselection Malaria Therapy
Available online: 07 May 2018More LessThe pharmacokinetics (PK) and ex vivo activity (pharmacodynamics [PD]) of two artemisinin combination therapies (ACTs) (artemisinin–piperaquine [ARN–PPQ] [Artequick®] and artesunate–amodiaquine [ARS–AQ] [Coarsucam™]) in healthy Vietnamese volunteers were compared following 3-day courses of the ACTs for the preselection of the drugs for falciparum malaria therapy. For PK analysis, serial plasma samples were collected from two separate groups of 22 volunteers after ACT administration. Of these volunteers, ex vivo activity was assessed in plasma samples from seven volunteers who received both ACTs. The area under the concentration–time curve (AUC0–∞) was 3.6-fold higher for dihydroartemisinin (active metabolite of ARS) than that for ARN, whereas the AUC0–∞ of desethylamodiaquine (active metabolite of AQ) was 2.0-fold lower than that of PPQ. Based on the 50% inhibitory dilution values of the volunteers’ plasma samples collected from 0.25 to 3 hours after the last dose, the ex vivo activity of ARS–AQ was 2.9- to 16.2-fold more potent than that of ARN–PPQ against the drug-sensitive D6 Plasmodium falciparum line. In addition, at 1.5, 4.0, and 24 hours after the last dose, the ex vivo activity of ARS–AQ was 20.8-, 3.5-, and 8.5-fold more potent than that of ARN–PPQ against the ARN-sensitive MRA1239 line. By contrast, at 1.5 hours, the ex vivo activity of ARS–AQ was 5.4-fold more active than that of ARN–PPQ but had similar activities at 4 and 24 hours against the ARN-resistant MRA1240 line. The PK–PD data suggest that ARS–AQ possesses superior antimalarial activity than that of ARN–PPQ and would be the preferred ACT for further in vivo efficacy testing in multidrug-resistant falciparum malaria areas.
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Case Report: Probable Case of Spontaneous Encephalopathy Due to Loiasis and Dramatic Reduction of Loa loa Microfilariaemia with Prolonged Repeated Courses of Albendazole
Available online: 07 May 2018More LessLoiasis is a vector-borne parasitic disease caused by the filarial nematode Loa loa and transmitted by the tabanid vectors from the genus Chrysops. Loa loa infection is associated with clinical manifestations such as pruritus, migratory transient edema, passage of adult worm in the bulbar conjunctiva, retinal damage, glomerular damage, albuminuria, pleural effusion, hydrocele, and endomyocardial fibrosis. Data reporting the occurrence of spontaneous encephalopathy associated with loiasis are very scanty. Severe adverse events occurring post-ivermectin administered in the framework of the fight against onchocerciasis and/or lymphatic filariasis in loiasis co-endemic areas have been closely associated with very high L. loa microfilariaemia. Different regimens have been used to lower L. loa microfilariaemia before definitive treatment, and many discrepancies have been reported. We report the case of a patient who was admitted to a health facility and hospitalized for 34 days for altered consciousness, blurred vision, headache, and chills. After other potential diagnoses were eliminated, the patient was confirmed with encephalopathy due to loiasis and referred to the Centre for Research on Filariasis and other Tropical Diseases (CRFilMT). On admission at CRFilMT, the patient was harboring 28,700 microfilariae per milliliter of blood (mf/mL), and after four 21-day courses of 400 mg daily albendazole, the L. loa microfilariaemia lowered to 5,060 mf/mL. The patient was then treated with ivermectin 3 mg and a total clearance of microfilariae was observed, with satisfactory clinical evolution and no adverse event. This case study further confirmed that albendazole is effective against L. loa, but might necessitate a longer course.
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The Hidden Burden of Plasmodium vivax Malaria in Pregnancy in the Amazon: An Observational Study in northwestern Brazil
Available online: 07 May 2018More LessWe measured the prevalence of malaria in pregnancy and estimated its impact on birth weight and length and maternal hemoglobin in 1,180 women from Juruá Valley, the main malaria hotspot in Brazil. Antenatal malaria episodes, 74.6% of them due to Plasmodium vivax, were microscopically diagnosed in 8.0% of the women and were associated with an average reduction in birth weight z-scores of 0.35 (95% confidence interval [CI] = 0.14–0.57) and in birth length z-scores of 0.31 (95% CI = 0.08–0.54), compared with malaria-free pregnancies. Affected mothers had a mean decrease in hemoglobin concentration at delivery of 0.33 g/100 mL (95% CI = 0.05–0.62 g/100 mL); 51.6% were anemic. The timing and frequency of antenatal infections influenced pregnancy outcomes and first- or second-trimester infections were not associated with decreased birth weight and length and maternal hemoglobin at delivery. Although repeated antenatal vivax infections were associated with poorer birth outcomes, even a single vivax malaria episode was associated with a significant reduction in birth weight and length and maternal hemoglobin. Overall, 7.5% women had the parasite’s DNA found in peripheral blood at delivery. Most (83.1%) of these 89 perinatal infections were due to P. vivax and only 7.9% of them progressed to symptomatic disease after delivery. Plasmodium vivax and Plasmodium falciparum DNA was found in 0.6% and 0.3% of 637 cord blood samples examined, respectively, but only one newborn developed clinical neonatal malaria. Our results further challenge the notion that vivax malaria is relatively benign during pregnancy and call for better strategies for its prevention.
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Case Report: Hemianopia: From Suspected Glioblastoma to the Diagnosis of Ectopic Schistosomiasis Haematobium Infection in a Traveler Returning from the Republic of the Congo
Available online: 30 April 2018More LessSchistosomiasis due to Schistosoma haematobium is a widespread disease usually affecting the urinary tract associated with hematuria and kidney disorders. Neurological damage is rarely reported and symptoms are nonspecific and may suggest brain tumors such as glioma. We describe the first double ectopic haematobium schistosomiasis case involving the brain and intestine.
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Increased Human Incidence of West Nile Virus Disease near Rice Fields in California but Not in Southern United States
Authors: Tony J. Kovach and A. Marm KilpatrickAvailable online: 30 April 2018More LessAnthropogenic land use change, including agriculture, can alter mosquito larval habitat quality, increase mosquito abundance, and increase incidence of vector-borne disease. Rice is a staple food crop for more than half of the world’s population, with ∼1% of global production occurring within the United States (US). Flooded rice fields provide enormous areas of larval habitat for mosquito species and may be hotspots for mosquito-borne pathogens, including West Nile virus (WNV). West Nile virus was introduced into the Americas in 1999 and causes yearly epidemics in the US with an average of approximately 1,400 neuroinvasive cases and 130 deaths per year. We examined correlations between rice cultivation and WNV disease incidence in rice-growing regions within the US. Incidence of WNV disease increased with the fraction of each county under rice cultivation in California but not in the southern US. We show that this is likely due to regional variation in the mosquitoes transmitting WNV. Culex tarsalis was an important vector of WNV in California, and its abundance increased with rice cultivation, whereas in rice-growing areas of the southern US, the dominant WNV vector was Culex quinquefasciatus, which rarely breeds in rice fields. These results illustrate how cultivation of particular crops can increase disease risk and how spatial variation in vector ecology can alter the relationship between land cover and disease.
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Amoxicillin Quality and Selling Practices in Urban Pharmacies and Drug Stores of Blantyre, Malawi
Authors: Ibrahim Chikowe, Sarah L. Bliese, Samuel Lucas and Marya LiebermanAvailable online: 23 April 2018More LessThis study evaluated a newly developed paper analytical device (PAD) for screening amoxicillin samples in Blantyre urban townships. Covert shoppers attempted to buy amoxicillin from a geographically stratified selection of private pharmacies (N = 22 out of 26) and drug stores (N = 23 out of 103) in the township area. According to the PAD results, all 42 samples obtained by the shoppers contained amoxicillin and none contained suspicious filler materials. Next, the products were assayed using high-performance liquid chromatography. Consistent with the PAD results, all samples contained the correct amount of amoxicillin with no unexpected ingredients. However, one sample was purchased as amoxicillin and contained that ingredient, but was packaged in capsules that are normally used to package ampicillin. Almost every sample failed a simple packaging analysis. Nine in 10 samples were missing their original packaging and/or inserts (52.4% repackaged capsules and 35.7% repackaged blister packs). Only 33.3% of the packages had expiry dates, 16.7% had batch numbers, and 47.6% had the manufacturer’s name. Dispensing practices were likewise unsatisfactory. Ninety-five percentage of the sellers sold the amoxicillin without a prescription, even though this medicine is regulated as prescription-only in Malawi. Although the chemical analysis showed that amoxicillin quality was good, our market survey revealed poor adherence to prescription-only medicine dispensing of antibiotics, which threatens antimicrobial stewardship efforts. Furthermore, the wide prevalence of repackaging deprives medicines of important information needed during patient’s use, regulatory investigations, and pharmacovigilance reporting.
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Diagnostic and Treatment Monitoring Potential of A Stool-Based Quantitative Polymerase Chain Reaction Assay for Pulmonary Tuberculosis
Available online: 23 April 2018More LessA quantifiable, stool-based, Mycobacterium tuberculosis (Mtb) test has potential complementary value to respiratory specimens. Limit of detection (LOD) was determined by spiking control stool. Clinical test performance was evaluated in a cohort with pulmonary tuberculosis (TB) (N = 166) and asymptomatic household TB child contacts (N = 105). Stool-quantifiable polymerase chain reaction (qPCR) results were compared with sputum acid-fast bacilli (AFB) microscopy, GeneXpert MTB/RIF (Xpert MTB/RIF), and cultures. In Mtb stool-spiking studies, the LOD was 96 colony-forming units/50 mg of stool (95% confidence interval [CI]: 84.8–105.6). Among specimens collected within 72 hours of antituberculosis treatment (ATT) initiation, stool qPCR detected 22 of 23 (95%) of culture-positive cases. Among clinically diagnosed cases that were Xpert MTB/RIF and culture negative, stool qPCR detected an additional 8% (3/37). Among asymptomatic, recently TB-exposed participants, stool PCR detected Mtb in two of 105 (1.9%) patients. Two months after ATT, the Mtb quantitative burden in femtogram per microliters decreased (Wilcoxon signed-rank P < 0.001) and persistent positive stool PCR was associated with treatment failure or drug resistance (relative risk 2.8, CI: 1.2–6.5; P = 0.012). Stool-based qPCR is a promising complementary technique to sputum-based diagnosis. It detects and quantifies low levels of stool Mtb DNA, thereby supporting adjunct diagnosis and treatment monitoring in pulmonary TB.
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Case Report: Ocular Microsporidiosis: Case in a Patient Returning from India and Review of the Literature
Available online: 23 April 2018More LessMicrosporidia are protists close to the kingdom of fungi that may cause eye infections. Most cases are reported in Asia and affect both immunocompromised and immunocompetent patients. Here, we report a rare case of microsporidial keratoconjunctivitis in an immunocompetent French patient 3 weeks after returning from India. In our patient, Weber trichrome staining of conjunctival scrapings revealed rounded elements approximately 1–3 μm in size. Conventional PCR analysis by ribosomal RNA subunit sequencing showed 100% identity with Vittaforma corneae. Treatment by corneal debridement combined with fluoroquinolone eye drops allowed complete resolution of the lesions. Although rare, ocular microsporidiosis should be investigated in a patient who is native to Asia or has returned from an endemic area and presents with keratoconjunctivitis of undetermined etiology.
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Bunyavirus Taxonomy: Limitations and Misconceptions Associated with the Current ICTV Criteria Used for Species Demarcation
Authors: Bradley J. Blitvich, Barry J. Beaty, Carol D. Blair, Aaron C. Brault, Gerhard Dobler, Michael A. Drebot, Andrew D. Haddow, Laura D. Kramer, Angelle Desiree LaBeaud, Thomas P. Monath, Eric C. Mossel, Kenneth Plante, Ann M. Powers, Robert B. Tesh, Michael J. Turell, Nikos Vasilakis and Scott C. WeaverAvailable online: 23 April 2018More LessThe International Committee on Taxonomy of Viruses (ICTV) has implemented numerous changes to the taxonomic classification of bunyaviruses over the years. Whereas most changes have been justified and necessary because of the need to accommodate newly discovered and unclassified viruses, other changes are a cause of concern, especially the decision to demote scores of formerly recognized species to essentially strains of newly designated species. This practice was first described in the seventh taxonomy report of the ICTV and has continued in all subsequent reports. In some instances, viruses that share less than 75% nucleotide sequence identity across their genomes produce vastly different clinical presentations, possess distinct vector and host associations, have different biosafety recommendations, and occur in nonoverlapping geographic regions are classified as strains of the same species. Complicating the matter is the fact that virus strains have been completely eliminated from ICTV reports; thus, critically important information on virus identities and their associated biological and epidemiological features cannot be readily related to the ICTV classification. Here, we summarize the current status of bunyavirus taxonomy and discuss the adverse consequences associated with the reclassification and resulting omission of numerous viruses of public health importance from ICTV reports. As members of the American Committee on Arthropod-borne Viruses, we encourage the ICTV Bunyavirus Study Group to reconsider their stance on bunyavirus taxonomy, to revise the criteria currently used for species demarcation, and to list additional strains of public and veterinary importance.
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Necrotizing Pneumonia Caused by Chromobacterium violaceum Soil Bacterium: Report of a Rare Human Pathogen Causing Disease in a Previously Undiagnosed Immunodeficient Child
Authors: Alean Frawley, Lauren Powell, John R. McQuiston, Christopher A. Gulvik and Rodolfo E. BéguéAvailable online: 23 April 2018More LessChromobacterium violaceum is a rare, potentially serious pathogen. Most clinicians have no experience with its clinical appearance or treatment. We describe a case of a child presenting with necrotizing pneumonia caused by C. violaceum. We describe case complexities, including the need for a multidisciplinary approach to diagnosis and treatment.
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Gametocyte Development and Carriage in Ghanaian Individuals with Uncomplicated Plasmodium falciparum Malaria
Available online: 23 April 2018More LessPlasmodium falciparum gametocytes develop over 9–12 days while sequestered in deep tissues. On emergence into the bloodstream, they circulate for varied amounts of time during which certain host factors might influence their further development. We aimed to evaluate the potential association of patient clinical parameters with gametocyte development and carriage via in vivo methods. Seventy-two patients were enrolled from three hospitals in the Volta region of Ghana in 2016. Clinical parameters were documented for all patients, and gametocyte prevalence by microscopy was estimated at 12.5%. By measuring RNA transcripts representing two distinct gametocyte developmental stages using reverse transcriptase quantitative PCR (RT-qPCR), we obtained a more precise estimate of gametocyte carriage while also inferring gametocyte maturation. Fifty-three percent of the study participants harbored parasites expressing transcripts of the immature gametocyte-specific gene (PF3D7_1477700), whereas 36% harbored PF3D7_1438800 RNA-positive parasites, which is enriched in mid and mature gametocytes, suggesting the presence of more immature stages. Linear logistic regression showed that patients older than 5 years but less than 16 years were more likely to carry gametocytes expressing both PF3D7_1477700 and PF3D7_1438800 compared with younger participants, and gametocytemia was more likely in mildly anemic individuals compared with those with severe/moderate anemia. These data provide further evidence that a greater number of malaria patients harbor gametocytes than typically estimated by microscopy and suggest a possible association between age, fever, anemia, and gametocytemia.
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Babesia microti and Malaria Infection in Africa: A Pilot Serosurvey in Kilosa District, Tanzania
Authors: Evan M. Bloch, Kasubi Mabula, Andrew Levin, Zakayo Mrango, Jerusha Weaver, Beatriz Munoz and Sheila K. WestAvailable online: 09 April 2018More LessBabesia is a tick-borne intraerythrocytic parasite that is clinically and diagnostically similar to malaria parasite, conferring risk of misdiagnosis in areas where both parasites are endemic. Data on Babesia in humans in Africa are lacking, despite evidence that it is present in regional animal populations. Samples that were collected in November 2014 to July 2015 in Kilosa district, Tanzania, were evaluated for evidence of malaria and Babesia infection. Clinical data and laboratory samples (i.e., hemoglobin, rapid diagnostic testing [RDT] for malaria, peripheral blood smear, and dried blood spots) from a routine survey were available for analysis. Dried blood spots were tested using an investigational ELISA against Babesia microti. A total of 1,030 children aged 1 month to < 5 years were evaluated; 186 (18.1%) were malaria RDT positive, 180 (96.8%) of whom had peripheral smears reviewed; 70/180 (38.9%) were smear positive for parasites. The median (inter quartile range) and range of B. microti ELISA signal to cutoff (S/C) ratio was 0.10 (0.06–0.15) and 0.01–1.65, respectively; the S/C ratios were significantly higher in subjects ≥ 1 year as compared with those < 1 year old (P < 0.001). There was also a statistically significant association between a positive RDT for malaria and the Babesia S/C (median 0.09 versus 0.13 in RDT negative versus RDT positive, respectively; P < 0.001). The highest S/C ratios were disproportionately clustered in a few hamlets. The findings suggest that Babesia may be present in Kilosa district, Tanzania. However, serological cross-reactivity and false positivity, notably between Babesia and Plasmodium spp., cannot be definitively excluded and have implications for testing in other settings.
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Association between Severity of Liver Disease, Frequency of Helicobacter pylori Infection, and Degree of Gastric Lesion in Egyptian Patients with Hepatitis B Virus Infection
Available online: 30 October 2017More LessThe relationship between hepatitis B virus (HBV) infection, severity of liver disease, frequency of Helicobacter pylori infection, and degree of gastric lesions was not yet fully investigated in Egyptian patients. The present work was performed on 100 Egyptian patients with HBV from the National Hepatology and Tropical Medicine Institute and 70 healthy volunteers as control group. The participants were subjected to full medical history taking, clinical examination, and laboratory investigations. All patients were positive for HBV surface antigen (HBV sAg), HBV DNA, and negative for hepatitis C virus antibodies. The severity of the liver disease was assessed using Child–Pugh scoring system. Screening of all participants for H. pylori Ag in stool was performed. Biopsy specimens were taken from the gastric lesions of H. pylori-infected patients for histopathological examination. The mean age of the patients and control group were 34.9 and 33.4 years, respectively. The levels of the liver enzymes were statistically higher in HBV patients than the control group. Helicobacter pylori Ag in stool was detected in 45.7% of the control group, and a higher percentage (60%) was detected in the patients group. Chronic gastritis with glandular atrophy and metaplasia was found in 15.6% of patients of Child–Pugh A, 70% of Child–Pugh B, and 100% of Child–Pugh C. It could be concluded that the prognosis of the liver disease significantly influences the severity of the gastric pathology in H. pylori infection.
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Molecular Identification of Onchocerca spp. Larvae in Simulium damnosum sensu lato Collected in Northern Uganda
Available online: 02 October 2017More LessPrevious studies have demonstrated that the presence of larvae of other filarial species in Simulium damnosum sensu lato can distort estimates of transmission potential for Onchocerca volvulus in West Africa. However, studies conducted in foci of onchocerciasis in West Central Uganda indicated that larvae other than O. volvulus were not common in vectors collected there. Recent data collected in Northern Uganda revealed a striking discordance between estimates of the prevalence of flies carrying O. volvulus infective larvae obtained from molecular pool screening and dissection methods. To resolve this discrepancy, sequences from three mitochondrially encoded genes were analyzed from the larvae collected by dissection. All larvae analyzed were Onchocerca ochengi v. Siisa, a parasite of cattle, or Onchocerca ramachandrini, a parasite of warthogs. These results suggest that nonhuman parasite larvae are common in vectors in Northern Uganda, underscoring the necessity for molecular identification methods to accurately estimate O. volvulus transmission.
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Dengue Virus Serotypes 1 and 2 Responsible for Major Dengue Outbreaks in Nepal: Clinical, Laboratory, and Epidemiological Features
Available online: 31 July 2017More LessDengue virus (DENV) is expanding toward previously nonendemic areas. DENV has recently been introduced in Nepal with limited information. We report the clinical features and serotype distribution of DENV in Nepal during the major outbreaks. A total of 1,215 clinical dengue cases at two major hospitals of central and western Nepal were investigated. Demographic, clinical, and laboratory parameters were recorded. Serum specimens were tested for DENV by IgM/IgG enzyme-linked immunosorbent assays (ELISAs) and reverse transcription polymerase chain reaction (RT-PCR). We confirmed DENV infection in 403 (33%) patients from 12 districts with an estimated case fatality rate of 1.5%. DENV infection was more common in adults (87%) and urban settings (74%). We detected all four serotypes but DENV-1 and -2 were mainly responsible for major outbreaks (92%). Overall, 60% of all DENV infections were secondary and 17% were severe dengue; both being more frequent among the DENV-2 infections. Rash, bleeding, abdominal pain, hepatomegaly, elevated liver enzymes, and thrombocytopenia were significantly more common in severe dengue compared with nonsevere infections. We also confirmed the expansion of dengue to hill urban areas (DENV-1 and -2), including the capital Kathmandu (altitude, 1,300 m) though > 90% cases were from southern plains. Differential clinical and laboratory features probably helps in clinical decisions. Multiple serotypes circulation and elevated secondary infections pose potential risk of severe outbreaks and deaths in the future. Therefore, a country with recent dengue introduction, like Nepal, urgently requires a systematic surveillance and appropriate control measures in place to respond any disastrous outbreaks.
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Evaluation of Community-Directed Operation of Black Fly Traps for Entomological Surveillance of Onchocerca volvulus Transmission in the Madi-Mid North Focus of Onchocerciasis in Northern Uganda
Available online: 31 July 2017More LessEntomological measures of transmission are important metrics specified by the World Health Organization to document the suppression and interruption of transmission of Onchocerca volvulus, the causative agent of onchocerciasis. These metrics require testing of large numbers of vector black flies. Black fly collection has relied on human landing collections, which are inefficient and potentially hazardous. As the focus of the international community has shifted from onchocerciasis control to elimination, replacement of human landing collections has become a priority. The Esperanza window trap (EWT) has shown promise as an alternative method for collection of Simulium damnosum s.l., the primary vector of O. volvulus in Africa. Here, we report the results of a community-based trial of the EWT in northern Uganda. Traps operated by residents were compared with human landing collections in two communities over 5 months. Three traps, when operated by a single village resident, collected over four times as many S. damnosum as did the two-men collection team. No significant differences were noted among the bait formulations. The results suggest that EWTs may be effectively operated by community residents and that the trap represents a viable alternative to human landing collections for entomological surveillance of O. volvulus transmission.
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Case Report: Old World Mucosal Leishmaniasis: Report of Five Imported Cases to the Hospital for Tropical Diseases, London, United Kingdom
Authors: Trupti A. Patel, Glenis K. Scadding, David E. Phillips and Diana N. LockwoodAvailable online: 24 July 2017More LessOld World species of Leishmania typically cause visceral and cutaneous leishmaniasis. Mucosal involvement is typically seen with infection by Leishmania species found in South America, usually after the healing of cutaneous leishmaniasis. We present five imported cases of mucosal leishmaniasis caused by Old World Mediterranean Leishmania infantum exclusively affecting the nasal mucosa or vocal cord. In only one case was there a recollection of a preceding cutaneous lesion compatible with cutaneous Leishmaniasis. Of significance was that four out of five cases were receiving local corticosteroids for chronic lung disorders and four were systemically immunosuppressed. This report highlights the importance of considering mucosal leishmaniasis in the differential diagnosis in those presenting with upper respiratory tract mucosal lesions with a relevant travel history to the Mediterranean and in whom malignancy has been excluded.
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