The American Journal of Tropical Medicine and Hygiene - Volume 102, Issue 1, January 2020

Residency programs are increasingly responding to the growing demand for global health (GH) education by forming dedicated GH tracks. These tracks incorporate a targeted curriculum, support best practices surrounding GH electives such as predeparture preparation and post-return debriefing, and encourage meaningful engagement with international and domestic partners. The University of Minnesota’s pediatric residency has had a formal GH track since 2005, and although they have shared several curricular components in the literature, they have yet to provide a comprehensive summary of their GH track. In this article, the authors provide a thorough description of their evolving GH track model, highlighting outcomes and sharing free resources, with the goal of providing a concise, replicable GH track framework for educators seeking to provide more formal GH education within residency programs.

Severe thrombocytopenia with impairment of the activity of platelets and impairment of blood clotting occurs in dengue hemorrhagic fever (DHF). Continuation of dual antiplatelet therapy in such patients can result in life-threatening hemorrhages. On the other hand, withholding of antiplatelets in a patient undergone coronary stenting lately can lead to stent thrombosis, resulting in myocardial infarctions and sudden cardiac death. There are no guidelines on management of DHF in patients with coronary stents. Here, we discuss about several divergent factors that need to be considered and balanced when managing such patients. We describe a case as an example to illustrate how we balanced the risk of serious bleeding versus the risk of stent thrombosis successfully according to evolution of the disease process, by temporary withholding of antiplatelets in such a patient.

Pneumonia is one of the leading causes of death in children under 5 years worldwide. In resource-limited settings, WHO recommendations state that pneumonia can be presumptively diagnosed through the presence of cough and/or difficult breathing and a respiratory rate (RR) that is higher than age-specific cutoffs. As a new diagnostic aid the children’s automated respiration monitor (ChARM) can automatically measure and classify RR in children under 5 years, but the effect of its chest attachment on the RR has not been studied. The aim of this study was to understand if misclassification of the true RR occurred by ChARM attachment. Two hundred eighty-seven children at a health center in South Ethiopia were screened for eligibility, with 188 children aged 2–59 months enrolled in the study. The RR was measured manually before and 1, 3, and 5 minutes after ChARM attachment. The proportion of children with fast or normal RR classification at baseline and the change between RR classifications over time were analyzed. Eight (4.9%; 95% CI 2.1, 9.4) of 163 children changed RR classification from normal to fast between the baseline RR count and the 1 minute RR count. Results from this study suggest that ChARM has a minor influence on the RR of children immediately after attachment, in most cases without clinical importance.

Globally, diarrheal and respiratory infections are responsible for more than 24% of deaths in children aged less than 5 years. Historically, these disease entities have been studied separately; recent evidence suggests that preceding diarrheal disease may be a risk factor for subsequent respiratory illness. We used data from a community-based, prospective randomized trial of maternal influenza immunization of 3,693 pregnant women and their 3,646 infants conducted in rural Nepal from 2011 to 2014. A case-crossover design was used to determine whether the risk of respiratory infection in the 30 days following a diarrheal episode was increased compared with that 30 days prior. Diarrheal illness was a significant risk factor for subsequent respiratory illness in infants but not in women during pregnancy or in women up to six months postpartum. Diarrheal illness and respiratory infections remain important global sources of morbidity and mortality, and our study supports a causal relationship between them in infants.

There are hundreds of millions of internal migrants in China, and tuberculosis (TB) is an important health threat to them. However, the mental health problems of internal migrants with TB in China have been ignored. The present study aimed to determine the prevalence of depressive symptoms and its associated risk factors among internal migrants with TB in China. A cross-sectional survey was conducted between June 2018 and March 2019 in Shenzhen, southern China. Data were collected from 1,057 internal migrants with TB using a structured questionnaire. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale. Multinomial logistic regression analysis was used to identify risk factors for depressive symptoms. Of the 1,057 participants included in this study, 53.8% had depressive symptoms. Of these, 38.9% had mild, whereas 14.9% had moderate-to-severe depressive symptoms. Multinomial logistic regression analysis suggested that higher likelihoods of depressive symptoms were associated with female gender, lower education, family dysfunction, poor doctor–patient communication, and TB-related stigma. This study shows that the prevalence of depressive symptoms among internal migrants with TB is high in China. Targeting interventions and treatment of depressive symptoms among internal migrants with TB are needed.

Mycobacterium africanum (MAF) is known to endemically cause up to 40–50% of all pulmonary TB in West Africa. The aim of this study was to compare MAF with Mycobacterium tuberculosis (MTB) with regard to time from symptom onset to TB diagnosis, and clinical and radiological characteristics. A cross-sectional study was conducted in Bamako, Mali, between August 2014 and July 2016. Seventy-seven newly diagnosed pulmonary TB patients who were naive to treatment were enrolled at Mali’s University Clinical Research Center. Sputum cultures were performed to confirm the diagnosis and spoligotyping to identify the mycobacterial strain. Univariate and multivariate analyses were used to identify factors associated with disease progression. Overall, the frequency of female patients was 25% in MAF infection and only 10.0% in MTB infection (OR = 2.9), and MAF was more represented in patients aged ≥ 30 years (57.1% versus 36.7% [OR = 2.3]). More MAF- than MTB-infected patients had a history of a prior TB contact (32.1% versus 14.3% [OR = 2.8]). The mean duration between cough onset and TB diagnosis was 111 days (∼3.7 months) for MAF and 72 days (∼2.4 months) for MTB (P = 0.007). In a multivariate regression, weight loss (body mass index [BMI] < 18.5 kg/m2) and cough duration (> 4 months) were strongly associated with MAF infection (OR = 5.20 [1.49–18.26], P = 0.010, and 4.74 [1.2–18.58], P = 0.02), respectively. Our data show that MAF infection was significantly associated with lower BMI and a longer time between symptom onset and TB diagnosis than MTB. This supports the concept that MAF infection may have slower disease progression and less severe cough symptoms than MTB.

In addition to the complications of leprosy, people affected by leprosy (PALs) can suffer from chronic diseases. We evaluated the recent pattern of deaths among Korean PALs and compared it with that in the general population. We analyzed the death certificate data of 1,359 PALs from 2010 through 2013. The all-cause and cause-specific standardized mortality ratio (SMR) and standardized mortality with 95% CI were calculated. Malignancy had the highest standardized mortality, with 130.9 deaths per 100,000 persons, followed by cardiovascular diseases (CVDs; 85.5 deaths) and respiratory diseases (38.2 deaths). Of malignancies, liver cancer caused the greatest number of cancer deaths (40.0 deaths). The all-cause mortality of PALs was significantly lower than that in the general population, corresponding to an SMR of 0.84 (95% CI 0.79–0.88). Deaths from malignancy and CVDs were significantly lower, corresponding to SMRs (95% CIs) of 0.88 (0.79–0.98) and 0.75 (0.67–0.84), respectively. The death rates for lung and stomach cancers were lower, whereas mortality due to liver cancer was higher, with an SMR of 1.79 (95% CI 1.43–2.22). Except for liver cancer and infection, the causes of mortality of PALs tend to be lower than that in the general population. The most common underlying cause of death in PALs was stroke, followed by ischemic heart disease, liver cancer, and pneumonia.

The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, redeveloped as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera-induced diarrhea in adult volunteer challenge trials but has not been studied in children in developed countries. We performed a phase 4, placebo-controlled, double-blind, multicenter study to assess the safety, immunogenicity, and tolerability of a single, oral dose of PXVX0200 in children and adolescents aged 6–17 years in the United States and bridged immunogenicity to adults aged 18–45 years from a separate lot consistency study. Volunteers were randomized to receive a single dose of 1 × 109 colony forming units (CFU) of PXVX0200 or placebo. Immunogenicity endpoints included SVA levels on days 1, 11, and 29 in volunteers aged 6–17 years and also on days 91 and 181 in volunteers aged 12–17 years. Safety was assessed by comparing solicited signs and symptoms on days 1–8, unsolicited adverse events (AEs) through day 29, and serious AEs through day 181. A total of 374 participants were enrolled, comprising 321 vaccine and 53 placebo recipients. The SVA seroconversion rates 10 days after immunization were 98.6% and 2.1% in vaccine and placebo recipients, respectively, and the vaccine seroconversion rate was non-inferior to the 93.5% rate seen in adults aged 18–45 years. Most reactogenicity was mild to moderate, and there were no vaccine-related serious AEs. The complete dose was consumed in 95.3% and 98.1% of vaccine and placebo recipients, respectively. PXVX0200 appears safe, immunogenic, and well tolerated in children and adolescents aged 6–17 years.

Nontyphoidal Salmonella infections can result in bacteremia. This study was undertaken to determine the predictive factors for bacteremia in children aged less than 16 years. Medical data were collected for every child with positive nontyphoidal Salmonella cultures in blood or stools at the University hospital of Martinique, French West Indies, between January 2005 and December 2015. Among 454 patients, 333 were included; 156 cases had confirmed bacteremia, and 177 were included as control group with nontyphoidal Salmonella only isolated in stools. Age at diagnosis, delay before consulting, prematurity, immunosuppression, or hyperthermic seizures were not significantly associated with bacteremia. C-reactive protein was higher in cases of bacteremia (P = 0.01); however, after adjusting to the threshold of 30 mg/L, there was no longer any difference. There were also significant relations for electrolytes such as hyponatremia (odds ratio (OR) = 2.08 [95% CI = 1.31–3.95]; P < 0.01), high urea level (OR = 0.53 [95% CI = 0.32–0.88], P < 0.01). The infecting serotype was the most discriminant risk factor (P < 10−4). Among 28 serotypes isolated between 2005 and 2015, Salmonella panama was the most common serotype: 122 strains (78.2%) were isolated from bacteremic patients versus 60 (33.9%) from nonbacteremic patients (P < 10−4). Salmonella panama was the most important risk factor for bacteremia (OR = 7.37 [95% CI = 3.18–17.1], P < 10−4) even after multivariate analysis (OR = 13.09 [95% CI = 5.42–31.59], P < 10−4). After adjusting for bacteremia, S. panama was associated with a significantly higher body temperature than other Salmonella: 39°C (standard deviation [SD] = 0.92) versus 38.2°C [SD = 1.1], linear regression P < 10−3. Children with Salmonella serotype panama infection were at higher risk of bacteremia than children infected with other Salmonella serotypes.

Scrub typhus is a life-threatening zoonotic disease, which is caused by Orientia tsutsugamushi, an obligatory intracellular Gram-negative bacterium. It is transmitted by Leptotrombidium mites in endemic regions of Southeast Asia. So far, data on imported scrub typhus cases to non-endemic areas and immunological descriptions are rare. Eleven scrub typhus cases that had been diagnosed by the German National Reference Center for Tropical Pathogens between 2010 and 2018 were retrospectively reviewed for clinical symptoms, laboratory changes, and travel destinations. Patient sera were included if follow-up samples showed simultaneous seroconversion for IgM and IgG antibody responses by immunofluorescence assays or concurrence with the first serum sample. The median of seroconversion was week 2 after symptom onset. Cytokine levels were measured over time, demonstrating simultaneously upregulated major Th1, Th2, and Th17 cytokines in the acute phase of infection followed by normalization during convalescence. This study underlines the complex mixed cytokine response elicited by scrub typhus and highlights clinical and diagnostic aspects of imported infections with O. tsutsugamushi.

Angiostrongylus cantonensis is a zoonotic, parasitic nematode causing angiostrongyliasis or rat lungworm disease. Clinical diagnosis in humans is currently confirmed by detection of parasite DNA in cerebrospinal fluid. This study estimated human exposure to A. cantonensis in volunteer participants solicitated via public venues on east Hawai’i Island using blood-based tests. Antibodies were screened in sera by crude antigen ELISA, followed by a 31-kDa dot-blot test developed and validated in Thailand. Human participants (n = 435) donated blood samples and completed a questionnaire to self-report relevant symptomology or clinical diagnosis. Among symptoms reported by participants diagnosed by licensed clinicians, headaches, high eosinophil counts, stiff neck, fatigue, and joint pain were most severe during the initial 3 months of infection. ELISA results revealed 22% of the serum samples as positive, 46% as equivocal, and 32% as negative. A subset of 186 samples was tested by dot blot, with 30% testing positive and 70% testing negative. A significantly higher mean ELISA value was found among recently (2014–2015) clinically diagnosed participants as than among those with a diagnosis before 2010 (P = 0.027). All dot-blot positives were also ELISA positive and were significantly associated with higher ELISA values compared with dot-blot negatives (P = 0.0001). These results suggest that an ELISA using crude antigen isolated from adult A. cantonensis from Hawai’i may be an effective initial screening method for estimating exposure to A. cantonensis in Hawai’i and likewise suggest that dot-blot tests using the 31-kDa antigen exhibit efficacy as a diagnostic for exposure.

Subarachnoid neurocysticercosis (SUBNCC) is usually caused by an aberrant proliferative form of Taenia solium causing mass effect and arachnoiditis. Thirty of 34 SUBNCC patients were treated with extended cysticidal and anti-inflammatory regimens and followed up a median of 4.2 years posttreatment (range: 15 for ≥ 4 years, 20 ≥ 2 years, 26 > 1 year, and 3 < 1 year). The median ages at the time of first symptom, diagnosis, and enrollment were 29.7, 35.6, and 37.9 years, respectively; 58.8% were male and 82.4% were Hispanic. The median time from immigration to symptoms (minimum incubation) was 10 years and the estimated true incubation period considerably greater. Fifty percent also had other forms of NCC. Common complications were hydrocephalus (56%), shunt placement (41%), infarcts (18%), and symptomatic spinal disease (15%). Thirty patients (88.2%) required prolonged treatment with albendazole (88.2%, median 0.55 year) and/or praziquantel (61.8%; median 0.96 year), corticosteroids (88.2%, median 1.09 years), methotrexate (50%, median 1.37 years), and etanercept (34.2%, median 0.81 year), which led to sustained inactive disease in 29/30 (96.7%) patients. Three were treated successfully for recurrences and one has continuing infection. Normalization of cerebral spinal fluid parameters and cestode antigen levels guided treatment decisions. All 15 patients with undetectable cestode antigen values have sustained inactive disease. There were no deaths and moderate morbidity posttreatment. Corticosteroid-related side effects were common, avascular necrosis of joints being the most serious (8/33, 24.2%). Prolonged cysticidal treatment and effective control of inflammation led to good clinical outcomes and sustained inactive disease which is likely curative.

Cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of the cestode Echinococcus granulosus. The parasite typically infects dogs and ungulates, with humans acting as dead-end hosts. Information on the epidemiology of CE is lacking from Central Asia, including from Kazakhstan where CE cases are reported centrally. This study presents data from the Kazakhstan Scientific and Practical Center for Sanitary and Epidemiological Evaluation and Monitoring on CE patients treated surgically, with a diagnosis confirmed by pathology. Evaluation of data from 2007 to 2016 indicated that the CE incidence rate decreased during this time period in most areas of Kazakhstan (country-level incidence rate of 5.6 versus 4.7 cases/100,000 population in 2007 and 2016, respectively). Cystic echinococcosis had a higher incidence in southern Kazakhstan, with an incidence rate between 7.0 and 10.5 cases per 100,000 population, whereas northern regions had rates less than 4.0 cases per 100,000 population. Moreover, despite the overall decrease, CE incidence continues to increase in the south. Cystic echinococcosis surveillance is needed, particularly in the south, to help inform policymakers and orient disease control efforts.

Fear of adverse events (AEs) negatively affects compliance to mass drug administration (MDA) for lymphatic filariasis (LF) elimination program. Systemic AEs are believed to occur because of killing of microfilariae, whereas localized soft tissue reactions might be due to the death of adult worms following therapy. Most AEs are mild and self-limited. However, localized AEs are sometimes more significant and of concern to participants. Here, we describe localized AEs that were noted during a large community study that evaluated the safety of a triple-drug regimen (ivermectin, diethylcarbamazine, and albendazole) for the treatment of LF in India. We have also discussed the importance of timely detection and careful management of AEs for preserving community confidence in MDA.

Schistosoma mansoni infection negatively impacts children’s physical health and may influence general well-being. Schistosomiasis control programs aim at reducing morbidity through mass drug administration (MDA). This study aimed to compare morbidity markers between two cohorts of Tanzanian schoolchildren with initial high prevalence of S. mansoni infection. One cohort (N = 254 at baseline) received annual MDA for 4 years using community-wide treatment (CWT). The second cohort (N = 318 at baseline) received school-based treatment (SBT) every other year for 4 years. At year 5, the CWT cohort and the SBT cohort were reduced to 153 and 221 children, respectively. The characteristics of the 198 children lost to follow-up did not differ at baseline from those who were examined in year 5. Schistosoma mansoni infection, hemoglobin (Hb) and anemia, physical fitness, and perceived quality of life were investigated at baseline, year 3, and year 5, whereas liver and spleen pathology (ultrasound) were investigated only at baseline and year 5. Cohorts were compared using two-way mixed-model analysis of variance (ANOVA). Both treatment regimens significantly decreased individual-level mean intensity of S. mansoni infection, anemia, and hepatomegaly, and increased Hb levels after 5 years. Hepatomegaly was the only parameter affected by the treatment regimen as the CWT approach reduced the percentage of individuals with hepatomegaly significantly more than the SBT approach. Both treatment regimens led to reduced physical fitness at year 5 compared with baseline. The modest impact of the two control strategies are probably due to initial low intensity of infection, ensuring low level of schistosomiasis-related morbidity.