The American Journal of Tropical Medicine and Hygiene - Current Issue

Catastrophic damage and floods followed the deadliest cyclone on record for the Southern Hemisphere. In the aftermath of Cyclone Idai, a cholera outbreak was detected. The global stockpile of oral cholera vaccine was rapidly deployed to counter this fast-growing epidemic. We urge the international community to continue to highlight the importance of water, sanitation, and hygiene as the long-term goal for controlling cholera and meeting the 2030 Sustainable Development Goals.

Ethiopia’s hepatitis C virus (HCV) prevalence is predicted to rise by 2030. To halt this increasing trend, a suitable approach to the elimination of HCV is needed. This review explores the current status, challenges, and opportunities and outlines a strategy for the micro-elimination approach in Ethiopia. I searched PubMed and EMBASE using combined Medical Subject Heading databases for the literature on HCV micro-elimination. A phased public health approach to HCV micro-elimination, including preparation/capacity building (phase I), implementation (phase II), and rollout and scale-up (phase III), targeting people living with HIV, prisoners, chronic hepatitis and cancer patients, blood donors, and pregnant women is a pragmatic strategy to Ethiopia. This can be implemented at general and tertiary care referral hospitals with a future scale-up to district hospitals through task-shifting by training general practitioners, nurses, laboratory technologists, and pharmacists. Availability of the highly effective direct-acting antivirals (DAAs) can be ensured by expanding the existing program that provides highly subsidized DAAs through an agreement with Gilead Sciences, Inc. and eventually aiming at domestic generic manufacturing. The significant enablers to HCV micro-elimination in Ethiopia include the control of healthcare–associated HCV infection, blood safety, access to affordable testing and pan-genotypic DAAs, task-shifting, multisectoral partnership, and regulatory support. General population-based HCV screening and treatment are not cost-effective for Ethiopia because of high cost, program complexity, and disease epidemiology.

Aedes mosquitoes are the principal dengue vector in Taiwan, where the use of insecticides is a key element in the national control strategy. However, control efforts are constrained by the development of resistance to most insecticides, including pyrethroids. In this study, mutations in the voltage-gated sodium channel (VGSC) gene resulting in knockdown resistance (kdr) were examined in Aedes aegypti. Fragments of the VGSC gene were polymerase chain reaction (PCR)-amplified followed by restriction fragment length polymorphism analysis in samples from various settings in Southern Taiwan covering dry and wet seasons from 2013 to 2015. Three kdr mutations were identified: V1023G, D1794Y, and F1534C, with observed frequencies of 0.36, 0.55, and 0.33, respectively, in the dry season of 2013–2014. Exploring for temporal changes, the most important observation was the 1534C allele frequency increment in the following season to 0.60 (P < 0.05). This study suggests that continued insecticide pressure is driving the mutational changes, although the selection is ambiguous in the mosquito population.

Perceived exposure to mosquitoes plays a fundamental role in the adoption of a range of protective behaviors aiming to prevent and control mosquito-borne disease. However, it is largely unknown in the present literature to what extent perceived exposure is associated with actual exposure. Moreover, the perception of nuisance may depend on the natural environment in which human populations are living, and especially its epidemiological context. In this study, the hypothesis that perceived exposure is driven by mosquito abundance was tested in two different geographic areas. We compared a range of perceived nuisance measures—collected through questionnaires—with egg number measured within ovitraps located in the south of France, which has been recently colonized by an arbovirus vector, and La Martinique island, a tropical French territory, which has a long history of outbreaks of mosquito-borne pathogens. Unexpectedly, only the nuisance due to mosquito noise was correlated with ovitrap activity in southern France. All other perceived exposure measures, both in the south of France and in Martinique, were not correlated with egg number surrounding households investigated. These results suggest the existence of habituation effects that may disturb the engagement in adaptive behaviors in the face of change in the entomological conditions.

It remains uncertain why most infectious disease mortalities disappeared before modern medical interventions. Historical epidemiology using prospectively collected U.S. Army data from the Civil War (1860–1861), Spanish–American War (1898–1899), and First World War (1917–1918) suggests that epidemiological isolation was a major mortality risk factor for soldiers. Morbidity and mortality due to common infections decreased progressively from 1860 to 1918, except for influenza during the 1918 pandemic. Adult measles or mumps infections are indicative of isolated rural populations and correlated with disease mortality by U.S. state. Experiencing infections before adulthood may equip the immune system to better resist infections and decrease mortality rates.

Hundreds of thousands of children continue to die each year from diarrhea. We piloted a low-cost liquid chlorine point-of-use (POU) water treatment among elementary school children in Bangladesh. We began the 1-month intervention in four schools (two urban and two rural) by introducing POU drinking water hardware and behavior change communication. We trained teachers to deliver sessions encouraging students to drink chlorinated water from their own small plastic bottles to avoid disease transmission. We used cue cards and flip charts as visual aids. We evaluated the acceptability, feasibility, and potential for sustainability after 1 month and after 14 months of the intervention. During 1-month follow-up, among 141 drinking events observed, 141 students (100%) drank chlorinated water. In 93 or 66% of events, students used their own bottles, and in 43 (30%) of the events, they used common cups or hands washed before drinking. During the 14-month follow-up, we observed 732 drinking events. In 653 of 732 events (89%), students drank chlorinated water; in 78 events (11%), they consumed water from untreated drinking water sources. Among those who consumed chlorinated water, 20% (131/653) used their own bottles to drink water, 72% (467/653) used common cups, and 8% (55/653) used both hands to drink water. Most stated that they drank chlorinated water because it is safe, it has health benefits, and treatment reduces germs. Introduction of specific hardware, weekly hygiene sessions, and education materials enabled schools to treat water at POU and students to consume treated water.

This study was performed to examine whether prenatal lipid-based nutrient supplementation is an effective means of improving birth outcomes compared with other types of supplementation including iron folic acid (IFA), United Nations multiple micronutrient preparation (UNIMAP), other multiple micronutrients (MMN), and fortified corn–soy blend (CSB). A meta-analysis was performed to determine the relative risks and mean differences in birth outcomes between prenatal lipid-based nutrients versus prenatal IFA, UNIMAP, other MMN, and CSB in randomized controlled trials. Eleven databases, including PubMed (MEDLINE), were searched. Study quality was assessed using the Cochrane Collaboration’s tool for assessing the risk of bias. Fifty-eight overall good-quality studies extracted from 11 eligible articles with 101,553 mother–baby pairs were included. Lipid-based nutrient supplementation significantly reduced the risks of low birthweight, small for gestational age, and stunting (n = 5, 5, and 4, respectively) and significantly increased the means of birthweight, birth length, arm circumference, and weight-for-age z-score (n = 5, 5, 4, and 3, respectively). Lipid-based nutrient supplementation did not significantly reduce the risk of preterm birth, stillbirth, abortion, perinatal death, or underweight (n = 5, 5, 5, 3, or 3, respectively) or significantly increase the mean of head circumference or height-for-age z-score (n = 4 or 2, respectively). In conclusion, the results supported the efficacy of prenatal lipid-based nutrient supplementation compared with IFA, UNIMAP, other MMN, and CSB for reducing the risk of small birth size.

Between 1990 and 2015, Kenya had a 0.9% annual reduction in maternal mortality, one of the lowest reductions globally. This slow decline was linked to the relatively low utilization of delivery services. We designed a mobile phone–enhanced 24-hour transport navigation system coupled with personalized and interactive gestation-based text messages (MAccess) to address maternal child health service utilization. The primary purpose of this analysis is to explore the ways in which pregnant and postnatal women made decisions regarding care-seeking for pregnancy and childbirth services, the processes of getting care from home to the hospital as well their perceptions on how the MAccess intervention affected their pregnancy and childbirth care-seeking and utilization experience. We conducted semistructured, individual interviews with 18 postpartum women. Participants were purposively sampled. Interviews were audiotaped, transcribed, and analyzed using thematic analysis. For participants in this study, all three delays interacted in a complex manner to affect women’s utilization of pregnancy and childbirth services. Even though women were aware of the benefits of skilled birth attendance, other health system factors such as opening hours, or health workers’ attitudes still deterred women from delivering in health facilities. The MAccess innovation was highly acceptable to women throughout pregnancy and childbirth and helped them navigate the complex and layered individual, infrastructural, and health system factors that put them at risk of adverse maternal and newborn outcomes. These findings emphasize that an integrated approach, which addresses all delays simultaneously, is important for reducing perinatal morbidity and mortality.

Stunting, defined as height-for-age Z score equal to or lower than −2, is associated with increased childhood mortality, cognitive impairment, and chronic diseases. The aim of the study was to investigate the relationship between linear growth, intestinal damage, and systemic inflammation in infants at risk of stunting. We followed up 78 infants aged 5–12 months living in rural areas of Peru for 6 months. Blood samples for biomarkers of intestinal damage (intestinal fatty-acid–binding protein [I-FABP] and zonulin) and systemic inflammation (interleukin-1β, interleukin-6, tumor necrosis factor α [TNF-α], soluble CD14, and lipopolysaccharide-binding protein [LBP]) and fecal samples for microbiome analysis were collected at baseline and closure of the study. The children’s growth and health status were monitored through biweekly home visits by trained staff. Twenty-one percent of the children became stunted: compared with non-stunted children, they had worse nutritional parameters and higher levels of serum I-FABP at baseline. The likelihood of becoming stunted was strongly associated with an increase in sCD14 over time; LBP and TNF-α showed a trend toward increase in stunted children but not in controls. The fecal microbiota composition of stunted children had an increased beta diversity compared with that of healthy controls throughout the study. The relative abundance of Ruminococcus 1 and 2, Clostridium sensu stricto, and Collinsella increased in children becoming stunted but not in controls, whereas Providencia abundance decreased. In conclusion, stunting in our population was preceded by an increase in markers of enterocyte turnover and differences in the fecal microbiota and was associated with increasing levels of systemic inflammation markers.

Although the issue of substandard and falsified medicines is quite well known, most research has focused on medicines used to treat communicable diseases, and relatively little research has been carried out on the quality of medicines for noncommunicable diseases (NCDs). This study was designed to assess the quality of seven widely used medicines for NCDs in Cambodia during 2011–2013. Medicines were collected from private community drug outlets in Phnom Penh (urban area), by stratified random sampling and in Battambang, Kandal, Kampong Speu, and Takeo (rural areas) by convenience sampling. Samples were subsequently analyzed by visual inspection, authenticity investigation, and pharmacopoeial analysis by high-performance liquid chromatography. Various discrepancies were observed in visual inspection of packages and medicines. Of 372 tablet/capsule samples from 64 manufacturers in 16 countries, the manufacturers confirmed 107 (28.8%) as authentic; the authenticity of other samples could not be verified. Three hundred sixty-four (97.8%) samples were registered in Cambodia. Among all samples, 23.4% (95% CI 19.2–28.0) were noncompliant in one or more of the quality tests: 12.9% (95% CI 9.7–16.7) contained an amount of active pharmaceutical ingredient outside the permitted range, including some showing extreme deviations, 14% (95% CI 10.6–17.9) failed because of content variation, and 10.8% (95% CI 7.8–14.4) failed to meet pharmacopoeial reference ranges in dissolution tests. Pharmaceutical quality appeared to be unrelated to storage conditions. Although no sample was obviously falsified, there is a high prevalence of substandard medicines for NCDs in Cambodia, indicating the need for focused regulatory action, including collaborative initiatives with manufacturers.

In this study, we report on the prevalence of 19 virulence genes in enteroaggregative Escherichia coli (EAEC) isolates from northern South Africa. Stool samples obtained prospectively from 97 children from 1 to 12 months of age were analyzed, and EAEC isolates were confirmed based on the presence of aaiC or aatA genes. We investigated 177 enteroaggregative Escherichia coli isolates for the prevalence of virulence genes using multiplex polymerase chain reaction. The chromosomal gene aaiC was detected at higher frequency (48.0%) compared with aatA (26.0%). The gene encoding the open reading frame Orf61 was the most prevalent putative virulence trait detected among the isolates (150/177; 84.7%). None of the genes was statistically associated with diarrhea (P > 0.05). Detection rates were higher during 7–12 month of life with an association observed for the pic gene and the age group 7–12 months (P = 0.04). Winter was the season with the highest detection rates. Our data reveal a high prevalence of Orf61, Orf3, and astA in South African EAEC isolates. Specific genes may provide additional markers for the study of disease associations with age and season of sample collection.

Pneumonia, as defined by WHO, is a syndromic diagnosis characterized by presence of cough or difficult breathing. Presentation to health-care provider depends on timely identification of signs and symptoms by caretakers. We explored patterns of health-care utilization among caretakers of a randomly selected sample of 1,152 children aged 2–59 months, residing in low-income settlements of Karachi, Pakistan. Information on household demographics, occurrence of pneumonia-specific symptoms, care seeking, air quality, and knowledge regarding preventive measures for pneumonia was collected. Predictors of care seeking were estimated using weighted logistic regression. Prevalence of pneumonia with cough and rapid or difficulty in breathing was found to be 40.8% and 37.1% in infants (2–11 months) and children (12–59 months), respectively. Ninety-five percentage of caretakers sought care, 68.5% privately. Odds ratios (ORs) for independent predictors of care-seeking were as follows: younger age of child (infants compared with children), 3.60 (95% CI = 2.65–4.87); caretaker with primary education compared with none, 3.40 (2.46–4.70); vaccine awareness, 1.65 (1.45–1.87); and breastfeeding awareness, 1.32 (1.13–1.53). Presence of symptoms such as fever OR, 1.51 (1.30–1.76); tachypnea, 1.57 (1.35–1.83); chest indrawing, 2.56 (2.05–3.18); persistent vomiting, 1.69 (1.37–2.09); and recurrent illness, 2.57 (2.23–2.97) were also predictive. There is high health-care utilization for pneumonia with the skewed presentation toward private services. Strategies should be focused on making pneumonia care standardized, efficient and affordable, especially in the private sector.

Antimicrobial resistance (AMR) is a growing threat to global health. Although AMR endangers continued effectiveness of antibiotics, the impact of AMR has been poorly estimated in low-income countries. This study sought to quantify the effect of AMR on treatments for pediatric pneumococcal disease in Ethiopia. We developed the DREAMR (Dynamic Representation of the Economics of AMR) model that simulate children younger than 5 years who acquire pneumococcal disease (pneumonia, meningitis, and acute otitis media) and seek treatment from various health facilities in Ethiopia over a year. We examined the AMR levels of three antibiotics (penicillin, amoxicillin, and ceftriaxone), treatment failures, and attributable deaths. We used the cost-of-illness method to assess the resulting economic impact of AMR from a societal perspective by estimating the direct and indirect treatment costs and productivity losses. Findings showed that AMR against antibiotics that were used to treat pneumococcal disease led to 195,763 treatment failures per year, which contributed to 2,925 child deaths annually in Ethiopia. Antimicrobial resistance resulted in a first-line treatment failure rate of 29.4%. In 1 year, the proportion of nonsusceptible Streptococcus pneumoniae bacteria increased by 2.1% and 0.5% for amoxicillin and penicillin, and reduced by 0.3% for less commonly used ceftriaxone. Annual costs of AMR to treat pneumococcal disease were around US$15.8 million, including US$3.3 million for ineffective first-line treatments, US$3.7 million for second-line treatments, and US$8.9 million for long-term productivity losses. Antibiotic stewardship to reduce misuse and overuse of antibiotics is essential to maintain the effectiveness of antibiotics, and lessen the health and economic burden of AMR.

We report a case of acute rheumatic fever with severe pancarditis occurring simultaneously with probable acute post-streptococcal glomerulonephritis in a previously well, Australian Aboriginal, 29-year-old male. These autoimmune streptococcal sequelae are usually considered pathogenetically distinct, and concurrence has not previously been reported from this high-burden setting. We hypothesize that a single type of infecting group A Streptococcus (Strep A) triggered both autoimmune sequelae. Salient features included mitral and aortic regurgitation that worsened during the acute illness, painful pericarditis, and high troponin; severe acute kidney injury with oliguria, hematuria, and macroalbuminuria; reduced complement (C3); and elevated streptococcal serology. The case highlights important diagnostic and management challenges. It also illustrates the serious morbidity impact of the complications of Strep A.

Leprosy reactions are immune-mediated complications occurring in up to 50% of patients. The immune consequences of helminth infections and micronutrient deficiencies suggest a potential role in type 1 reactions (T1R) or type 2 reactions (T2R). We conducted a case–control study in Minas Gerais, Brazil, to evaluate whether comorbidities and other factors are associated with reactions in patients with multibacillary leprosy. Stool and serum were tested for helminth infections. Deficiencies of vitamin A, D, and iron were measured using serum retinol, 25-hydroxyvitamin D, and ferritin, respectively. Logistic regression models identified associations between reactions and helminth infections, micronutrient deficiencies, and other variables. Seventy-three patients were enrolled, 24 (33%) with T1R, 21 (29%) with T2R, 8 (15%) with mixed T1R/T2R, and 20 (27%) without reactions. Evidence of helminth infections were found in 11 participants (15%) and included IgG4 reactivity against Schistosoma mansoni, Strongyloides, and Ascaris antigens. Thirty-eight (52%) had vitamin D deficiency, eight (11%) had vitamin A insufficiency, 21 (29%) had anemia, and one (1.4%) had iron deficiency. Multivariable logistic regression showed no statistically significant associations between helminth coinfections and total reactions (adjusted odds ratios [aOR]: 1.36, 95% CI: 0.22, 8.33), T1R (aOR: 0.85, 95% CI: 0.17, 4.17), or T2R (aOR: 2.41, 95% CI: 0.29, 20.0). Vitamin D deficiency and vitamin A insufficiency were also not statistically associated with reactions. However, vitamin deficiencies and helminth infections were prevalent in these patients, suggesting a potential role for additional treatment interventions. Studying reactions prospectively may further clarify the role of comorbidities in the clinical presentation of leprosy.

Disseminated nontuberculous mycobacterial (NTM) infections usually occur in severely immunosuppressed patients. These infections may also occur in previously immunocompetent patients with acquired anti–interferon-gamma antibodies (anti–IFN-γ Abs). A previously healthy 33-year-old man presented with a 3-week history of cough and fever. Chest computed tomography showed air-space consolidation in the middle lobe of the right lung and enlargement of the supraclavicular, mediastinal, and hilar lymph nodes. Tissue samples obtained via mediastinoscopy showed granuloma formation with acid-fast bacteria; cultures from the tissue revealed Mycobacterium kansasii. Accordingly, a diagnosis of disseminated M. kansasii disease was made. The positive control tested negative in the QuantiFERON-TB Gold In-tube test, suggesting the presence of anti–IFN-γ Abs. The ELISA test for anti–IFN-γ Abs demonstrated an increased titer. Antimycobacterial drug treatments were initiated after diagnosis. His symptoms improved over 2 months, and he remains well on outpatient management. Disseminated M. kansasii disease is a very rare condition suggestive of immunosuppression. Testing for anti–IFN-γ antibodies might be important in all cases of disseminated M. kansasii disease.

Genitourinary tuberculosis (TB) is a rare but well-described form of extrapulmonary TB. We present a case of a 35-year-old man from Ethiopia with scrotal swelling and fever who was found to have epididymo-orchitis due to Mycobacterium tuberculosis. The patient presented to the hospital multiple times before undergoing operative debridement with fine needle aspiration and tissue biopsy to confirm the diagnosis. He improved with antituberculous therapy. Patients with TB risk factors presenting with epididymitis that is refractory to empiric antibiotic therapy warrant consideration of TB epididymitis. Our case demonstrates the high index of suspicion required to establish a diagnosis of genitourinary TB.

Primary rib cage tuberculosis (TB) is an infrequent form of presentation and represents 1% of all cases of osteoarticular TB. We report three cases of children who were previously healthy and who began with swelling of the anterior surface of the rib as initial manifestation of TB. The most important clinical presentations in this series were swelling and pain, with lytic lesions and a soft tissue mass in image studies simulating oncologic pathologies. Because none of the cases had positive epidemiological contact, TB was initially not considered, so the delay in diagnosis from the onset of symptoms was 4, 1, and 2 months, respectively. The diagnosis was made through histomorphological analyses. Treatment was administered during 12, 10, and 9 months. Posttreatment studies did not show any evidence of extrapulmonary TB and until date, the patients remained without relapse or active disease. The findings in our cases illustrate that the diagnosis of chest wall TB should be suspected in all patients from endemic areas who present rib injury.

This follow-up cross-sectional study aimed to analyze the prevalence rate and risk factors related to latent tuberculosis infection (LTBI) and active tuberculosis (TB) in children aged < 15 years in contact with adults with smear-positive pulmonary TB (PTB) in a Brazilian municipality. Data were collected from interviews, clinical evaluations, chest X-rays, tuberculin skin tests, and interferon gamma release assays. The median time elapsed between diagnosis of the index case (IC) and inclusion in the study was 2.5 years (interquartile range [IQR] = 1.5–4.4) and 7.4 years (IQR = 3.8–9.7) when we reassessed the development (or not) of active TB. The median age at the time of exposure to the IC was 6.6 years (IQR = 3.3–9.4) and 14.1 years (IQR = 8.9–17.7) at the last follow-up. Of the 99 children and adolescents in contact with smear-positive PTB, 21.2% (95% CI = 14.0–29.9) were diagnosed with LTBI, and none developed active TB. There was no statistically significant difference between the LTBI and non-LTBI groups regarding demographic, socioeconomic, and epidemiological characteristics. Unlike national and international scenarios, we found a lower frequency of LTBI and no active TB among our studied patients. For better understanding of these findings, further studies might add, among other factors, host and Mycobacterium tuberculosis genetic features.

Intravenous (IV) dexamethasone is recommended for 14 days in stage 1 and 28 days in stage 2/3 tuberculous meningitis (TBM). We used a different steroid protocol. We shifted TBM patients to oral steroids after 48 hours of sustained improvement on IV steroids (oral group). Patients who worsened after shifting to oral steroids were reinitiated on IV steroids. Once they showed a consistent improvement for 48 hours, the IV steroids were overlapped with oral steroids for 7–10 days to taper off IV steroids (overlap group). We compared total IV steroid days in our patients with the recommended treatment and identified predictors that favored the oral group. This was a retrospective study. We included 98 patients with TBM (66 in the overlap group and 32 in the oral group) from January 2013 to July 2018. The median IV steroid days were 9 days (interquartile range of 4–12; 2–3.5 days in the oral group and 10–11.5 days in the overlap group). The mortality rate was 6.1%. The logistic regression model showed that TBM patients with basal exudate, tuberculoma, and modified Rankin scale (mRS) < 3 had a higher probability for going to the oral group. We conclude that total IV steroid days can be reduced in TBM patients by our method of steroid use. Presence of basal exudates and tuberculoma may favor early shifting from IV to oral steroid, whereas higher mRS may require a relatively longer course of IV steroid.

Tick-borne diseases (TBDs) are a growing public health threat and are increasingly identified as the cause of undifferentiated febrile illness. There is a significant gap in our understanding of ticks and their associated pathogens in Ecuador. An arboviral surveillance study allowed us to explore potential exposure to TBDs in febrile subjects. We tested plasma samples from 222 febrile subjects for spotted fever group rickettsial (SFGR) antibodies from southern coastal Ecuador in 2014–2015 via ELISA. Fifty-five (25%) subjects had evidence of anti-SFRG IgG or IgM antibodies. Although attempts to detect Rickettsia species in plasma by polymerase chain reaction were unsuccessful, these preliminary data suggest the possibility of endemic SFGR transmission in Ecuador. To better understand the burden and entomological risk for TBDs in Ecuador, future studies should expand TBD surveillance in humans, document common human-biting ticks, and measure pathogen carriage rates in questing ticks.

Rocky Mountain spotted fever (RMSF), caused by Rickettsia rickettsii, is a severe tick-borne infection endemic to the Americas. Oral doxycycline is effective, but during severe life-threatening disease, intravenous therapy is recommended. Unfortunately, intravenous formulations of doxycycline are not always available. Therefore, we aimed to determine the susceptibility of R. rickettsii to an alternative parenteral agent, tigecycline, in vitro and in vivo. To determine the minimum inhibitory concentration of tigecycline, R. rickettsii–inoculated Vero cells were incubated with medium containing tigecycline. At various time points, monolayers were collected and R. rickettsii was quantified via real-time polymerase chain reaction (PCR). The growth of R. rickettsii was inhibited in the presence of ≥ 0.5 µg/mL of tigecycline. To determine the effectiveness of tigecycline in vivo, guinea pigs were inoculated with R. rickettsii. Five days after inoculation, they were treated twice daily with subcutaneous tigecycline 3.75 mg/kg or subcutaneous doxycycline 5 mg/kg. Treated animals improved, whereas untreated controls remained ill. Tissues were collected for quantitative PCR–determined bacterial loads on day 8. Median bacterial loads in the tigecycline group were less than those in untreated animals: liver (0 versus 2.9 × 104 copies/mg), lung (0 versus 8.3 × 103 copies/mg), skin (2.6 × 102 versus 2.2 × 105 copies/mg), spleen (0 versus 1.3 × 104 copies/mg), and testes (0 versus 1.0 × 105 copies/mg, respectively). There were no significant differences in the bacterial loads between doxycycline-treated versus tigecycline-treated guinea pigs. These data indicate that tigecycline is effective against R. rickettsii in cell culture and in an animal model of RMSF.

Severe fever with thrombocytopenia syndrome is a tick-borne viral disease, with a high mortality rate that was first reported in China in 2009. Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, a bacterium transmitted to humans through chigger mite bites. Severe fever with thrombocytopenia syndrome and scrub typhus are endemic to South Korea. To investigate evidence of severe fever with thrombocytopenia syndrome virus (SFTSV) infection or mixed infection with scrub typhus in South Korea, we examined 2,329 sera samples collected from patients presenting from November 1, 2000, to November 1, 2003, for the diagnosis of rickettisal diseases at Seoul National University, Seoul, South Korea. We found retrospective evidence of SFTSV infection or mixed infection with scrub typhus in South Korea in 2000–2003. Severe fever with thrombocytopenia syndrome virus infections in South Korea occurred before previously reported cases and were more concurrent with those in China. It is important to consider SFTSV infection in patients with scrub typhus.

Paracoccidioidomycosis (PCM) is an endemic systemic mycosis that is of great importance in Latin America. Its occurrence in solid organ transplantation (SOT) is rare, but with high mortality rate. In this report, we describe a case of PCM in a liver transplant recipient 19 months after transplantation. The patient presented with multiple skin abscesses, arthritis, osteolytic lesions, and pulmonary and adrenal involvement. Despite the presence of disseminated disease and the patient’s immunosuppressed condition, the patient responded well to prolonged antifungal treatment with no sequelae, thus suggesting that early diagnosis and correct treatment may lead to favorable outcomes in SOT recipients with PCM.

Mucocutaneous leishmaniasis (MCL) is a rare infection caused by several species within the genus Leishmania. We present a patient with multifocal MCL masquerading as idiopathic midline granulomatous disease, featuring the unusual complication of ocular leishmaniasis, as a result of prolonged immunosuppressive therapy. We review clinical features, diagnosis, and treatment of this syndrome.

Cutaneous leishmaniasis (CL) is a major health problem worldwide. Although CL is a common disease among children, treatment regimens for the pediatric age group are based on extrapolation of efficacy data in adults. The present study aimed to evaluate the treatment outcome of CL in preschool-age children and the factors influencing the outcome. Two hundred ninety-four children were diagnosed with CL between December 2018 and March 2019 in Sinjar Province, Iraq. All patients were treated with intralesional injections of sodium stibogluconate and followed up for 3 months after the completion of treatment. The treatment success rate was 99% (291/294). A statistically significant association was found between the number of doses per lesion and the number of lesions (P = 0.002; CI = 0.066–0.2875). No association was found between the number of lesions, age, gender, or the presence of livestock and the treatment outcome. In conclusion, treatment success rate was high with the use of intralesional injection of sodium stibogluconate. A significant association was found between the number of lesions and the number of doses. Further studies are required to assess the treatment outcome indicators, including the genotype of leishmania.

Human African trypanosomiasis (HAT) also known as sleeping sickness is targeted for elimination as a public health problem by 2020 and elimination of infection by 2030. Although the number of reported cases is decreasing globally, integration of HAT control activities into primary healthcare services is endorsed to expand surveillance and control. However, this integration process faces several challenges in the field. This literature review analyzes what is known about integrated HAT control to guide the integration process in an era of HAT elimination. We carried out a scoping review by searching PubMed and Google Scholar data bases as well as gray literature documents resulting in 25 documents included for analysis. The main reasons in favor to integrate HAT control were related to coverage, cost, quality of service, or sustainability. There were three categories of factors influencing the integration process: 1) the clinical evolution of HAT, 2) the organization of health services, and 3) the diagnostic and therapeutic tools. There is a consensus that both active and passive approaches to HAT case detection and surveillance need to be combined, in a context-sensitive way. However, apart from some documentation about the constraints faced by local health services, there is little evidence on how this synergy is best achieved.

Surveillance of Chagas in the United States show more is known about prevalence in animals and vectors than in humans. Leveraging health information technology (HIT) may augment surveillance efforts for Chagas disease (CD), given its ability to disseminate information through health information exchanges (HIE) and geographical information systems (GISs). This systematic review seeks to determine whether technological tracking of Trypanosoma cruzi–infected domestic and/or sylvatic animals as sentinels can serve as a potential surveillance resource to manage CD in the southern United States. A Boolean search string was used in PubMed and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). Relevance of results was established and analysis of articles was performed by multiple reviewers. The overall Cohen statistic was 0.73, demonstrating moderate agreement among the study team. Four major themes were derived for this systematic review (n = 41): animals act as reservoir hosts to perpetuate CD, transmission to humans could be dependent on cohabitation proximity, variations in T. cruzi genotypes could lead to different clinical manifestations, and leveraging technology to track T. cruzi in domestic animals could reveal prevalent areas or “danger zones.” Overall, our systematic review identified that HIT can serve as a surveillance tool to manage CD. Health information technology can serve as a surveillance tool to manage CD. This can be accomplished by tracking domestic and/or sylvatic animals as sentinels within a GIS. Information can be disseminated through HIE for use by clinicians and public health officials to reach at-risk populations.

The discovery and characterization of novel parasite antigens to improve the diagnosis of Trypanosoma cruzi by serological methods and for accurate and rapid follow-up of treatment efficiency are still needed. TcTASV is a T. cruzi–specific multigene family, whose products are expressed on the parasite stages present in the vertebrate host. In a previous work, a mix of antigens from subfamilies TcTASV-A and TcTASV-C (Mix A + C) was sensitive and specific to identify dogs with active infection of high epidemiological relevance. Here, TcTASV-A and TcTASV-C were assayed separately as well as together (Mix A + C) in an ELISA format on human samples. The Mix A + C presented moderate sensitivity (78%) but high diagnostic accuracy with a 100% of specificity, evaluated on healthy, leishmaniasic, and Strongyloides stercoralis infected patients. Moreover, antibody levels of pediatric patients showed—2 years posttreatment—diminished reactivity against the Mix A + C (P < 0.0001), pointing TcTASV antigens as promising tools for treatment follow-up.

Although Ethiopia has an overall lower prevalence of Plasmodium falciparum among countries in Africa, the emergence of drug resistance could seriously hinder elimination efforts. Using samples collected from five therapeutic efficacy studies conducted in 2007–11, we evaluated the prevalence of putative drug resistance mutations in the pfcrt, pfmdr1, and kelch13 genes at the time of those studies, as well as the ama1 gene for genetic relatedness using a pooled amplicon deep sequencing approach. Among all sites, the kelch13 gene showed no mutations, whereas the pfcrt CVIET genotype was fixed in all populations. By contrast, the mdr1 gene demonstrated frequencies of resistant genotypes ranging from 10 to 100% at amino acid position 86 and from 0% to 57.8% at amino acid position 1246. Although we observed a low degree of haplotype sharing between sites, we did observe considerable haplotype sharing within sites over time. This suggests that P. falciparum populations in Ethiopia are isolated and able to persist through time.

Microscopy-determined Plasmodium falciparum positivity rates exceeding 10% on day 3 after initiation of artemisinin-based combination therapy (ACT) is an important indicator of artemisinin resistance. However, microscopy does not detect low-density parasitemia, contrary to molecular tools such as loop-mediated isothermal amplification (LAMP) and polymerase chain reaction (PCR). We compared microscopy, LAMP, and PCR for detection of P. falciparum on day 3 after ACT in 256 patients with uncomplicated malaria in Bagamoyo District, Tanzania. Day 3 positivity rates were 0%, 84.8%, and 84.4% for each method, respectively. The sensitivity and specificity of LAMP against PCR was 100% (95% CI, 96.1–100) and 77.4% (95% CI, 58.9–90.4) when quantitative PCR-determined parasite densities were ≥ two parasites/µL. Loop-mediated isothermal amplification had comparable diagnostic accuracy to PCR and could potentially represent a field-friendly tool for determining day 3 positivity rates. However, what day 3 P. falciparum positivity determined using molecular methods represents needs to be further elucidated.

Coinfections with malaria and soil-transmitted helminths (STHs) has been common among school-aged children in Tanzania. However, after a countrywide scaling up of interventions for malaria and STHs, there are limited data on the prevalence of malaria–STH coinfections and its effect on anemia in schoolchildren in Tanzania. We assessed the distribution and risk factors for malaria, STHs, and malaria–STH coinfections, and its relation to anemia among 445 primary schoolchildren in Muheza district. A semi-structured questionnaire was used to collect demographic characteristics of the children. Malaria rapid diagnostic test (mRDT) was used to diagnose malaria infection. Soil-transmitted helminths were diagnosed using the Kato–Katz technique. Primary outcome was anemia, defined as hemoglobin concentration < 11 g/dL. Chi-square (χ2) or Fisher’s exact tests, Kruskal–Wallis or t-test, and logistic models were used as appropriate. Overall, the prevalence of malaria, STHs, malaria–STH coinfection, and anemia were 18.4%, 6.1%, 1.6%, and 19.8%, respectively. Anemic children were more likely to have malaria (adjusted odds ratio [aOR] = 4.538, 95% CI: 2.189–9.409), whereas frequent use of bed nets was associated with reduced risk of malaria (aOR = 0.234, 95% CI: 0.130–0.42). On the other hand, not always using latrines and eating raw uncooked food increased the risk of STH infection. The prevalence of anemia was high and was associated with both malaria and malaria–STH infections, therefore calling for more integrated malaria–STH control approaches to target school-aged children.

Chronic infections with the food-borne liver flukes, Opisthorchis viverrini or Clonorchis sinensis, associate with cholangiocarcinoma, bile duct cancer, which generally has a poor prognosis. We have produced a rapid and simple immunochromatographic test (ICT) kit for the diagnosis of opisthorchiasis and clonorchiasis by the detection of IgG antibodies in human infection sera. Sera from volunteers with proven opisthorchiasis and several other parasitic diseases and from healthy controls were evaluated for the presence of liver fluke infection–specific antibodies using a preparation of excretory–secretory antigen from adult stage O. viverrini absorbed onto ICT strips. Diagnostic values were compared with an ELISA. The diagnostic sensitivity, specificity, and positive and negative predictive values of the ELISA were 100%, 98.3%, 97.9%, and 100%, whereas those for the ICT were 94.6%, 91.2%, 89.7%, and 95.4%, respectively. There was 91.7% concordance between the ICT with ELISA, and differences in performance between the tests were not statistically significant (P > 0.05). Twenty-seven of 30 (90%) of the clonorchiasis sera also were positive by ICT. This new ICT provides a facile, rapid test for point-of-care testing tool, which can be used at the bedside without the need for sophisticated equipment. Moreover, the ICT can be anticipated to supplement stool examination as a screening tool in the clinic for the diagnosis of opisthorchiasis and clonorchiasis, and in addition, it may be useful in screens of populations at risk of liver fluke infection–associated cholangiocarcinoma.

The prevalence of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide, including in regions where helminth infections such as the fish-borne liver fluke Opisthorchis viverrini (Ov) also occur. We investigated the effects of a high-fat and high-fructose (HFF) diet on the development and progression of NAFLD in experimental opisthorchiasis. Two groups of hamsters were infected with Ov for 4 months before the experiment to induce chronic inflammation. One of these groups (OvHFF) was fed with a HFF diet for up to further 4 months. One uninfected group of hamsters served as the normal control group, and another received the HFF diet (HFF group) for up to 4 months. Histopathology, biochemical parameters, and ultrastructural features of liver were investigated. In a short-term treatment, the OvHFF group showed significantly better homeostatic model assessment for insulin resistance level and lower liver lipid than did the HFF group. By contrast, histopathological characteristics of severe NAFLD were prominent in the OvHFF group after 4 months on the HFF diet, findings which were supported by confirmatory ultrastructural changes. In conclusion, opisthorchiasis induced the severe NAFLD in hamsters fed high-fat/high-fructose diets.

Human sparganosis is a cestode infection which is neglected as a differential diagnosis outside endemic countries. Diagnosis and therapy may be challenging depending on the clinical presentation and anatomic localization. The disease manifests predominantly as subcutaneous nodule(s) or intracranial mass lesion(s). Infection is primarily acquired by ingesting raw or undercooked amphibian or reptile flesh or by drinking water containing copepods. We report an unusual case of subcutaneous Spirometra erinaceieuropaei sparganosis presenting with two nonmigratory nodules in close proximity to each other on the right thigh of a Thai woman living in Switzerland.

A 50-year-old Chinese woman with a history of weakness and paroxysmal seizures of the left limb presented to our hospital with a ten-day history of neck pain. Imaging showed that there was a mass in the frontal lobe of her brain. On resection of the mass, a motile worm was identified. Morphological observation and molecular analysis of the mitochondrial COX1 and 28S rRNA genes of the worm extracted from the brain identified the causative agent as Spirometra mansoni. Homology search of the polymerase chain reaction (PCR)-amplified products from the case was conducted against gene fragments from local wild frogs. High homology was found between them, showing her likely exposure was frog consumption.

Strongyloidiasis, caused by Strongyloides stercoralis infection, is an important neglected tropical disease that causes significant public health problems in the tropics and subtropics. The disease can persist in hosts for decades and may be life-threatening because of hyperinfection and dissemination. Ivermectin (mostly) and albendazole are the most common anthelmintics used for treatment. Albendazole is suboptimal for this parasite, and although ivermectin is quite effective in immunocompromised patients, a multiple-course regimen is required. Furthermore, reliance on a single drug class for treating intestinal nematodes is a recipe for future failure. Therefore, it is important to discover new anthelmintics to treat or prevent human strongyloidiasis. One promising candidate is the Bacillus thuringiensis crystal protein Cry5B. Cry5B is highly potent against parasitic nematodes, for example, hookworms and Ascaris suum. Here, we investigated the potential of Cry5B against S. stercoralis. Multiple stages of S. stercoralis, including the first larval stage (L1s), infective stage (iL3s), free-living adult stage, and parasitic female stage, were all susceptible to Cry5B as indicated by impairment of motility and decreased viability in vitro. In summary, Cry5B demonstrated strong potential as an effective anthelmintic for treatment and transmission control of human strongyloidiasis, justifying further experiments to investigate in vivo therapeutic efficacy.