The American Journal of Tropical Medicine and Hygiene - Current Issue

Disseminated strongyloidiasis is often fatal, despite treatment with oral albendazole and parenteral ivermectin (IVM). Here, we report elevated plasma IVM and albendazole sulfoxide concentrations in the context of extracorporeal membrane oxygenation and continuous renal replacement therapy in a patient with disseminated strongyloidiasis treated with subcutaneous IVM and nasogastric albenzadole. Despite elevated drug plasma concentrations, live filariform larvae were detected in endotracheal aspirates after 2 weeks of treatment.

The aim of this study was to demonstrate the presence of Taenia solium eggs in beetles collected from sources within the natural environment through molecular techniques. Fifty-four pools of beetles were collected in three villages in Piura, Peru. DNA was extracted using the FastDNA spin kit for soil. Molecular identification of Taenia species was then performed through partial amplification of the mitochondrial cytochrome C oxidase subunit I gene. Finally, positive samples were sequenced to determine the tapeworm species. Seven positive samples were obtained through polymerase chain reaction amplification. Sequencing confirmed that two samples were from T. solium and three samples were from Taenia hydatigena. The other two samples could not be specifically identified. Our findings demonstrate that dung beetles ingest T. solium and T. hydatigena eggs under natural conditions and suggest that beetles may play a role in the dynamics of transmission of these cestodes.

Dipylidium caninum is a cosmopolitan cestode infecting dogs, cats, and humans. Praziquantel is a highly effective cestocidal drug and resistance in adult cestodes has not been reported. From 2016 to 2018, a population of dogs with cestode infections that could not be eliminated despite multiple treatments with praziquantel or epsiprantel was identified. Cases of D. caninum were clinically resistant to praziquantel and could not be resolved despite increasing the dose, frequency, and duration of treatment. Resistant isolates were identified and characterized by sequencing the 28S, 12S, and voltage-gated calcium channel beta subunit genes. Cases were only resolved following treatment with nitroscanate or a compounded pyrantel/praziquantel/oxantel product. Clinicians should be aware of this alarming development as treatment options for cestodes are limited in both human and veterinary medicine.

A 63-year-old woman who migrated from Nigeria to the United States was found to have an elevated total serum protein, anemia, and eosinophilia. Serum protein electrophoresis (SPEP) and serum protein immunofixation electrophoresis (SPIFE) demonstrated monoclonal immunoglobulin G (IgG) κ restricted bands (IgG 3,820 mg/dL; κ/λ ratio 4.47), indicative of monoclonal gammopathy of unknown significance (MGUS). A rapid diagnostic test (RDT) for malaria was positive for Plasmodium falciparum (BinaxNOW®; Alere Scarborough Inc., Scarborough, ME). Giemsa-stained blood smears were negative for malarial parasites, however, Loa loa microfilariae were identified. Reverse transcription polymerase chain reaction for P. falciparum, Plasmodium ovale, Plasmodium malariae, and Plasmodium vivax yielded a negative result. She was treated for loiasis with diethylcarbamazine and received no malaria medication. Treatment resulted in a resolution of the microfilaremia and eosinophilia, a negative RDT for malaria, and marked reduction in the monoclonal gammopathy. This is the first reported human case of MGUS associated with loiasis and its resolution after antiparasitic treatment.

Nodding syndrome (NS) is an encephalopathy characterized by the core symptom of epileptic head nodding seizures, affecting children at the age between 3 and 18 years in distinct areas of tropical Africa. A consistent correlation with onchocerciasis was found, but so far, the causation of NS has not been fully clarified. With a systematic analysis of features of a cohort of epilepsy patients examined in the Itwara onchocerciasis focus of western Uganda in 1994, we provide evidence that NS actually occurred in this area at this time, and we demonstrate a correlation between prevalence of NS and that of onchocerciasis in different villages. Following the elimination of onchocerciasis by community-directed treatment with ivermectin and ground larviciding, our data provide a baseline to examine the question whether NS will disappear once its putative cause has been removed.

We present a case of intussusception with complete small bowel obstruction caused by intestinal anisakidosis requiring surgical resection. A 30-year-old man presented with acute onset of severe abdominal pain 3 days after eating home-cured salmon gravlax. Despite surgery, the patient developed recurrent abdominal pain on two occasions with evidence of continued inflammation proximal to the surgical anastomosis. He was then treated with albendazole and prednisone, and symptoms improved. A decision was made to prophylactically treat two asymptomatic family members who also consumed home-cured gravlax with albendazole, resulting in one individual passing an intact Anisakis worm in her stool. We suggest that albendazole therapy could be considered as a therapy for continued symptoms of anisakidosis and postexposure prophylaxis of Anisakis larvae ingestion from a common source.

Burkholderia pseudomallei, the etiological agent of melioidosis, has been hypothesized to be endemic throughout the Caribbean, including the impoverished nation of Haiti. However, because of the protean clinical manifestations, presence of asymptomatic infections, and limited medical diagnostic capacity, the identification of active melioidosis cases remains challenging. A seroepidemiological study was conducted using a novel enzyme-linked immunosorbent assay (ELISA) to detect antibodies toward B. pseudomallei in the native population. The performance of an indirect ELISA with purified lipopolysaccharide (LPS) from B. pseudomallei was evaluated using serum collected from rhesus macaques exposed to aerosolized B. pseudomallei. After optimization, serum collected from asymptomatic population members (n = 756) was screened for polyvalent (immunoglobulin M [IgM]/ immunoglobulin G [IgG]/ immunoglobulin A) and monoclonal (IgG or IgM) immunoglobulins against B. pseudomallei LPS. The population seroprevalence was 11.5% (95% confidence interval [CI]: 9.2, 13.8) for polyvalent immunoglobulins, 9.8% (95% CI: 7.7, 11.9) for IgG, and 1.7% (95% CI: 0.8, 2.6%) for IgM. The seroprevalence was not significantly different by gender (P = 0.16), but increased significantly (P < 0.001) with age, yielding an estimated annual seroconversion rate of 1.05% (95% CI: 0.81, 1.3). The detection of both recent (IgM+) and previous (IgG+) exposure to B. pseudomallei provides serological evidence that melioidosis is endemic in Haiti.

Carrion’s disease is a neglected, vector-borne illness that affects Colombia, Ecuador, and especially Peru. The phlebotomine sand flies Lutzomyia verrucarum and Lutzomyia peruensis are the main illness vectors described, although other species may be implicated in endemic areas such as some northern Peruvian regions, in which Carrion’s disease vector has not been established. The aim of this study was to evaluate the presence of Bartonella bacilliformis DNA in Lutzomyia maranonensis from Cajamarca, northern Peru. This sand fly has not been defined as a vector yet. Centers for Disease Control and Prevention light traps were used to collect adult phlebotomine sand flies from 2007 to 2008 in the Cajamarca department. Female specimens were identified using morphological keys and were grouped into pools of five sand flies, taking into account district and sampling site (intradomicile or peridomicile). DNA was extracted, and then conventional and real-time polymerase chain reaction (RT-PCR) were performed to detect B. bacilliformis and subsequently confirmed by sequencing. A total of 383 specimens of L. maranonensis species were analyzed. Two of 76 pools were positive for B. bacilliformis by sequencing; all positives pools were from Querocotillo district. In addition, Mesorhizobium spp. were identified in two pools of sand flies, which is an α-proteobacteria phylogenetically very close to B. bacilliformis. This study presents molecular evidence that suggests L. maranonensis is naturally infected by B. bacilliformis in the Cajamarca department. Further research should determine if L. maranonensis is a vector and could transmit B. bacilliformis.

Tetanus, a vaccine-preventable and potentially fatal disease, continues to remain prevalent in low- and middle-income countries. Furthermore, physicians are often unfamiliar with management of severe tetanus without ventilator support. Therefore, we proposed a modified treatment protocol that provides a low-cost and effective solution for the management of severe tetanus in resource-constrained settings. This is an observational study of 42 patients with severe tetanus treated during 2015–2016 at Surya Kanta Hospital, Bangladesh. This facility does not have an intensive care unit (ICU), and patients admitted here were provided treatment with the modified protocol. A total number of 42 patients with severe tetanus were treated with the modified protocol. Among them, 24 (57.1%) recovered completely, six (14.3%) recovered with the sequela, and 12 (28.6%) died. Among those who recovered with the sequela, four needed mechanical support during walking and two had a visual impairment. No significant adverse event was recorded during the treatment period. The results gathered during this case series provide a sustainable, low-cost, and effective solution to management of severe tetanus in resource-constrained settings where ICUs are unavailable.

The escalating burden of infections attributable to methicillin-resistant Staphylococcus aureus (MRSA) in East African countries is calling for interventional strategies to control the spread of this strain. The present study aimed at determining the prevalence, antimicrobial profiles, and staphylococcal cassette chromosome mec (SCCmec) typing of MRSA strains. This was a cross-sectional laboratory-based study involving 226 non-duplicated S. aureus isolates from different clinical samples of patients attending a referral hospital in Kigali. Kirby–Bauer disk diffusion method was used for drug susceptibility testing. Methicillin-resistant S. aureus were confirmed using polymerase chain reaction (PCR) assay for the mecA gene and SCCmec type PCR assay was used for genotyping. Of 138 S. aureus, 39 (31.2%) were found to be MRSA strains. The mean age of the patients was 21.9 years. The incidence of MRSA increases with age and was 27.1% in patient age group younger than 18 years, 33.3% in the age group between 19 and 65 years, and 66.7% in patient age group older than 65 years. There was a significant association between geographic regions and incidence of MRSA (P = 0.02) with the high MRSA isolates from Northern (61.5%) and Western (50%) provinces. Methicillin-resistant S. aureus strains were found to be mostly susceptible to linezolid (93.5%). Among the MRSA strains, SCCmec type I and SCCmec type IV were the most prevalent at 56.4% and 17.9%, respectively. A high prevalence of MRSA was found in Rwanda. Staphylococcal cassette chromosome mec type I (52.2%) was the most predominant. A continuous surveillance of MRSA strains, particularly in the hospital settings, should be an enduring exercise in Rwanda.

Febrile illnesses are a major cause of mortality in sub-Saharan Africa. Early identification of patients at increased risk of death may avert adverse outcomes. We aimed to independently evaluate the performance of the Modified Early Warning Score, quick Sequential Organ Failure Assessment (qSOFA) score, and Integrated Management of Adolescent and Adult Illness (IMAI) emergency signs and severity criteria to predict in-hospital mortality among a prospective cohort of febrile patients in Tanzania. We evaluated 419 patients aged ≥ 10 years in the period 2007–2008. Of the 44 patients who died, 31 (70.5%) were human immunodeficiency virus (HIV) infected. On univariate analysis, in-hospital mortality was associated with HIV infection, oxygen saturation < 90%, respiratory distress, Glasgow Coma Scale < 15, neck stiffness, unconsciousness, convulsions, hemoglobin < 9 g/dL, absence of a systemic syndrome, and neurologic syndrome. A qSOFA score ≥ 2, the presence of at least one, two, or three IMAI emergency signs, and IMAI severe respiratory distress syndrome without shock were significantly associated with in-hospital mortality. The criterion “presence of at least one IMAI emergency sign” showed a good diagnostic accuracy, as highlighted by the high sensitivity, low negative likelihood ratio, and wide area under the receiver operating characteristics curve. The remaining scores showed a poor performance in predicting fatal outcomes in our study population. Further studies are needed to validate our findings and to derive early warning scores that have good clinical performance in settings throughout sub-Saharan Africa.

Different health-care management guidelines by the World Health Organization exist to help health workers in resource-limited settings treat patients. However, for children with unclassified fever and no danger signs, management guidelines are less clear and follow-up recommendations differ. Both a “universal follow-up” for all children, irrespective of health status, and a “conditional follow-up” only for children whose fever persists are recommended in different guidelines. It is unclear how feasible and acceptable these two different follow-up guidelines are among community health workers and caregivers of the sick child. This qualitative study was conducted in Ethiopia and was nested within a cluster-randomized controlled trial (cRCT). It aimed to determine health extension workers’ (HEWs’) and caregivers’ experiences of the management of febrile children and their perceptions of universal versus conditional follow-up recommendations. Seventeen HEWs and 20 caregivers were interviewed. The interviews revealed that HEWs’ understanding of how to handle an unclassified fever diagnosis increased with the implementation of the cRCT in both study arms (universal versus conditional follow-up). This enabled HEWs to withhold medicines from children with this condition and avoid referral to health centers. Both follow-up recommendations had perceived advantages, while the universal follow-up provided an opportunity to see the child’s health progress, the conditional follow-up advice allowed saving time and costs. The findings suggest that improved awareness of the unclassified fever condition can make HEWs feel more comfortable in managing these febrile children themselves and omitting unnecessary medication. Future community-level management guidelines should provide clearer instructions on managing fever where no malaria, pneumonia, diarrhea, or danger signs are present.

The transmission pattern of hemorrhagic fever with renal syndrome (HFRS) is associated with environmental conditions, including meteorological factors and land-cover. In the present study, the association between HFRS and environmental factors (including maximum temperature, relative humidity, rainfall, and normalized difference vegetation index) were explored in two typical counties in Northeast and two counties in Northwest China with severe HFRS outbreaks by using seasonal autoregressive integrated moving average model with exogenous variables (SARIMAX). The results showed that rainfall with 3- to 4-month lag was closely associated with HFRS in the two counties in Northeast China, whereas relative humidity with 1- or 5-month lag significantly impacts HFRS transmission in the two counties in Northwest China. Moreover, the SARIMAX models exhibit accurate forecasting ability of HFRS cases. Our findings provide scientific support for local HFRS monitoring and control, and the development of a HFRS early warning system.

Travelers to developing regions are at risk for development of influenza-like illness (ILI). Little is known of traveler and trip characteristics associated with the development of ILI. TravMil is a prospective observational study, enrolling subjects presenting to six military travel clinics or predeployment-screening sites. We analyzed pre- and post-travel surveys from travelers visiting regions outside of the continental United States, Western or Northern Europe, Canada, Australia, or New Zealand between January 2010 and March 2016. Influenza-like illness was defined as a self-reported fever associated with either sore throat or cough. Trip and traveler characteristics were analyzed to determine risk factors for the development of ILI. Two thousand nine hundred and thirty-two trips were recorded (55% male, median age 45 years, 69% white, 51% on vacation, median travel duration 17 days). The 2,337 trips included the number of self-reported influenza vaccinations in the preceding 5 years (median 5). Eleven percent of the trips were complicated by an ILI lasting a median of 5 days; 70% and 17% of these reported upper and lower respiratory tract infection, respectively, and 12% reported both. On multivariate analysis, increased risk of ILI was associated with female gender (odds ratio [OR]: 1.60 [confidence interval (CI): 1.25–2.05], P < 0.01), age (years) (OR: 1.01 [CI: 1.01–1.02], P < 0.01); and duration of travel (days) (OR: 1.01 [CI: 1.00–1.01], P < 0.01). Influenza-like illness is common in travelers, regardless of traveler characteristics, purpose of travel, destination, or season of year. Female gender, older age, and longer duration of travel were associated with an increased risk of ILI. Additional tools and strategies are needed to prevent ILI in international travelers.

Both social media use and the popularity of global health electives (GHEs) have increased in recent years. Social media use during GHE is commonplace and has benefits, yet sharers may not consider the ramifications of these posts, including privacy violations. Social media policies—which have become more common in residency programs—may aid in providing clear expectations to trainees abroad. The authors aimed to determine the prevalence of social media policies among pediatric residency programs that offer GHE. The authors used a cross-sectional survey design in which educators at pediatric residency programs that offer GHE were surveyed using REDCap®. For all quantitative data, proportions of responses were calculated and analyzed using Microsoft Excel 2013®. The authors analyzed qualitative data using a conventional content analysis approach. The survey was sent to 74 educators; 39 (53%) responses were received. Most (62%; n = 24) of the pediatric residency programs that offer GHE reported that their institution had a social media policy. About one-third (34%; n = 13) of respondents stated that their programs had social media guidelines that pertained specifically to GHE and fewer indicated that social media guidelines were included in their programs’ GHE predeparture curricula (32%; n = 12). This study found that most of the residency programs surveyed had social media guidelines, but few had guidelines applicable or specific to GHE. Informed by this study and a literature review, the authors propose template language for a social media guideline with considerations for social media use in the context of GHE.

Longitudinal and collaborative global health research curricula to train a well-versed global health corps through skills building in assessment and evaluation are lacking. A without-walls research curriculum was offered to medical and public health students between 2007 and 2015. Mentored cross-disciplinary research projects were developed and implemented in partnership with communities. A multilevel mixed methods design, including semi-structured interviews, post-curriculum surveys, presentations, publications, postgraduation metrics, and feedback from project sites, evaluated educational outcomes. Students (N = 25; aged 27 ± 1.9 years; 90.5% female) participated in the studies in 12 countries, resulting in 26 national-level presentations and 24 peer-reviewed publications, including per student average and range of Institutional Review Board submission (0.95; 0–3), poster presentation (0.85; 0–3), oral presentation (0.65; 0–2), and peer-reviewed submission (1.05; 0–4). On average, the studies (40% mixed methods) lasted 2 years. Analyses and manuscript writing were the most challenging; data collection and presentations were the most rewarding. Majority of the participants strongly agreed with achieving skills in community engagement, interviewing techniques, research design and implementation, research dissemination, and career development. Interview themes included expectations and learning goals, effective mentorship, impact on career goals, and ethical learning. Mentorship qualities were accessibility, real-time problem solving, research expertise, advocate, and balancing guidance with independence. Project sites’ feedback was overwhelmingly positive regarding the projects’ impact. Postgraduation participants hold positions in humanitarian organizations, research programs serving the underserved, and primary care residencies, fellowships, and faculty. This experience illustrates the feasibility and effectiveness of mentored global health research and underlines the crucial link between community collaboration and scholarship for effective global health practice.

Dengue encephalitis and dengue encephalopathy are frequent neurological complications of systemic dengue virus infection. Neuroimaging is normal in approximately 50% of patients. Common imaging abnormalities involve periventricular structures, including the basal ganglion, thalamus, and periventricular white matter. We describe an unusual case of dengue encephalopathy with unilateral imaging abnormalities involving the right cerebral hemisphere and mimicking the involvement of the right middle cerebral artery.

The management of dengue fever (DF) has been suggested to be categorized into decision groups A, B, and C; however, its usefulness in predicting mortality is still unclear, and hence we conducted this study to clarify this issue. We conducted a study by recruiting 2,358 patients with DF from the 2015 outbreak in the Chi-Mei Medical Center. Demographic data, vital signs, clinical symptoms and signs, coexisting morbidities, laboratory data, decision groups categorized according to World Health Organization for clinical management of dengue in 2012, and 30-day mortality rates were included for analysis. The overall 30-day mortality rate was 1.4%. The 30-day mortality rates in decision groups A, B, and C were 0%, 0.5%, and 46.2%, respectively. Compared with Group A, there was a higher mortality risk in Group C (odds ratio [OR]: 1,480, 95% confidence interval [CI]: 195–11,200). The area under the curve of the variable of Group C was excellent (OR: 0.92, 95% CI: 0.85–0.99). The sensitivity, specificity, positive predictive value, and negative predictive value for predicting 30-day mortality in Group C were 88.2%, 98.5%, 46.2%, and 99.8%, respectively. This study showed that decision Group C has a good predictive value for 30-day mortality. Further studies including validation in other nations are warranted.

Dengue is endemic in Indonesia. Here, we describe the epidemiology of dengue in the city of Yogyakarta, Central Java, as a prelude to implementation of a cluster-randomized trial of Wolbachia for the biocontrol of arboviral transmission. Surveillance records from 2006 to 2016 demonstrate seasonal oscillations of dengue incidence with varying magnitude. Two lines of evidence demonstrate a high force of infection; the hospitalized case burden of patients diagnosed with dengue hemorrhagic fever or dengue shock syndrome over the last decade consisted predominantly of children/adolescents, and a serosurvey of 314 healthy children aged 1–10 years found 68% possessed dengue virus–neutralizing antibodies. Finally, a mobility survey indicated children aged 1–10 years, and particularly 1–5 year-olds, spent most of their daytime hours at home. These findings inform the design of clinical trials to measure the impact of novel vector control methods such as Wolbachia introgression into Aedes aegypti mosquitoes, by providing baseline data on disease incidence and identifying subpopulations for recruitment into prospective studies of dengue virus infection and disease. The mobility survey findings indicate that in cluster trials of interventions applied at the community level, young children can reasonably be expected to spend most of their exposure time, in epidemiological terms, within the treatment arm to which they were randomized.

A clinical, serological, and molecular investigation was performed to determine the presence of dengue virus (DENV) and other flaviviruses among residents of the city of Reynosa, Tamaulipas, on the Mexico–U.S. border in 2014–2016. The sample population consisted of 2,355 patients with suspected dengue, in addition to 346 asymptomatic individuals recruited during a household-based epidemiological investigation designed to identify flavivirus seroconversions. Sera were collected from patients with suspected dengue in the acute phase of illness and from asymptomatic individuals at enrollment and every 5–7 months for 19 months. Sera from suspected dengue patients were tested for DENV antigen by enzyme-linked immunosorbent assay (ELISA), and select antigen-positive sera were further tested using a serotype-specific, quantitative reverse transcription–polymerase chain reaction. Sera from the household cohort were tested for flavivirus-reactive antibodies by immunoglobulin (Ig) M and IgG ELISAs using DENV antigen. A total of 418 (17.7%) patients with suspected dengue had laboratory-confirmed DENV infections, including 82 patients who were positive for DENV RNA. The most frequently detected serotype was DENV-1 (61 patients), followed by DENV-2 (16 patients) and DENV-3 (five patients). A total of 217 (62.7%) asymptomatic individuals had flavivirus-reactive antibodies at enrollment, and nine flavivirus-naïve individuals seroconverted. Sera from a subset of dengue patients and household participants, including all those who seroconverted, were further tested by plaque reduction neutralization test, resulting in the detection of antibodies to DENV-1, DENV-2, and West Nile virus. In summary, we provide evidence for the co-circulation of multiple flaviviruses in Reynosa, Tamaulipas, on the Mexico–U.S. border.