The American Journal of Tropical Medicine and Hygiene - Volume 101, Issue 5, November 2019

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.