The American Journal of Tropical Medicine and Hygiene - Current Issue

A previously healthy young man presented with a chronic cavitary pulmonary infection that began while in Goa, India. Burkholderia pseudomallei was cultured from sputum samples. The infection fully resolved after prolonged antibiotic treatment. Other than traveling during the monsoon season, extensive use of well-water for water-pipe smoking of cannabis was identified as a possible risk factor for infection. This is one of the first reports of travel-associated melioidosis from India. Genomic and immunological characterization suggested that the B. pseudomallei isolate collected from the reported case exhibited limited similarity to other B. pseudomallei strains.

Leptospirosis is the leading cause of zoonotic morbidity and mortality globally, yet little is known about the immune mechanisms that may contribute to pathogenesis and severe disease. Although neutrophils are a key component of early immune responses to infection, they have been associated with tissue damage and inflammation in some febrile infections. To assess whether neutrophils contribute to the pathogenesis observed in severe leptospirosis, we quantitated levels of neutrophil activation markers in patients with varying disease severities. Hospitalized leptospirosis patients had significantly higher levels of toll-like receptors 2 and 4 (TLR2 and TLR4, respectively) on peripheral neutrophils than healthy controls, with the highest levels detected in patients with organ dysfunction. We observed no significant differences in other neutrophil baseline activation markers (CD62L and CD11b) or activation capacity (CD62L and CD11b levels following stimulation), regardless of disease severity. Our results provide preliminary evidence supporting the hypothesis that higher initial bacterial loads or inadequate or delayed neutrophil responses, rather than TLR-driven inflammation, may drive severe disease outcomes.

Leishmaniasis is a vector-borne disease caused by protozoan parasites of the Leishmania genus. In Australia, leishmaniasis is an imported disease that is presenting itself at increased rates because of international travel, the influx of immigrants, and deployment of military operations to endemic regions. Although Leishmania species are morphologically indistinguishable, there is a strong correlation between some causative species of leishmaniasis and the subsequent response to the treatments available and patient outcome. Consequently, identification of the infective species is imperative as misidentification can result in the administering of an ineffective drug. The aim of this study was to develop a simple diagnostic tool with high sensitivity and specificity, which is capable of detecting the presence of the parasite and accurately differentiating the causative species in question. Using the advantageous properties of the maxi-circle kinetoplast DNA, a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) targeting the ND7 gene was developed for the analysis of imported cases of human leishmaniasis in Australia. Designed as a dual analysis, concurrent PCR of Leishmania maxi-circle DNA and digestion with two separate enzymes (NlaIII and HpyCH4IV), this study provides an appraisal on 24 imported cases of leishmaniasis between 2008 and 2017. Five Leishmania species were reported, with members of the Viannia subgenus being the most common. The implementation of novel diagnostic procedures for leishmaniasis such as the one reported here is needed to establish a gold standard practice for the diagnosis and treatment of leishmaniasis.

The subfamily Triatominae currently consists of 154 species, most of them being of great importance for public health because they are considered potential vectors of the protozoan Trypanosoma cruzi, the etiologic agent of Chagas disease. In addition to their epidemiological importance, these insects are considered important biological models for cell studies because they have peculiar characteristics in their cells, for example, persistence of the nucleolus during spermatogenesis. This phenomenon is characterized by the presence of the nucleolus or nucleolar corpuscles during all phases of meiosis. To date, all knowledge is restricted to the study of the presence/absence of the nucleolus during the triatomine meiosis, so the present work aimed to analyze if this persistent nucleolar material has transcriptional activity. Analysis of the meiotic metaphases of Rhodnius montenegrensis and Panstrongylus megistus by using fluorochrome acridine orange made it possible to characterize the presence of RNA in the nucleolar material. Thus, it was demonstrated, for the first time, that the persistent nucleolar material during triatomine meiosis is transcriptionally active, supporting the hypothesis of the relationship between nucleolar persistence during meiosis of these insects and the formation of the chromoid body, an organelle responsible for the support of all transcriptional activities during spermiogenesis.

Chagas disease is a public health problem caused by the Trypanosoma cruzi, and the T. cruzi I (TcI) and T. cruzi II (TcII) groups are considered important genotypes from the clinical point of view. Currently, the groups need to be molecularly analyzed for their identification; thus, we cytogenetically analyzed these groups with the objective of developing more accessible techniques for the characterization of these parasites. TcI and TcII groups were differentiated by nucleus characterization with lacto-acetic orcein (TcI—nucleus with positive heteropycnosis and TcII—nucleus with negative heteropycnosis), emphasizing the importance of the application of this technique for epidemiological and clinical studies of Chagas disease.

Angiostrongyliasis, caused by the Angiostrongylus cantonensis roundworm, became reportable in the state of Hawaii in 2007. We confirmed 82 reported cases between 2007 and 2017. There was a median of seven cases per year, and the majority (57%) of cases occurred between January and April. Most (83%) cases were found on the island of Hawaii, with geographic information system (GIS) analysis identifying hot spots on the east side of the island. However, cases were identified on the other major islands as well, suggesting the risk of exposure is present statewide. Comparisons of cases from 2007 to 2017 with cases from previous assessments found no statistical differences in cerebrospinal fluid results, peripheral blood results, or ages of cases. However, differences in geographic distribution of the cases were statistically significant. Improved testing and increasing awareness of the disease have contributed to our efforts to better understand the general risk factors and modes of transmission present in Hawaii and also helped improve our prevention efforts, although we still do not fully understand the specific causes of cases being concentrated in certain parts of the state over others. Continued outreach efforts, including public forums and publication of preliminary clinical guidelines, aim to inform and improve our public health response and efforts to prevent angiostrongyliasis.

Control of schistosomiasis presently relies largely on preventive chemotherapy with praziquantel through mass drug administration (MDA) programs. The Schistosomiasis Consortium for Operational Research and Evaluation has concluded five studies in four countries (Côte d’Ivoire, Kenya, Mozambique, and Tanzania) to evaluate alternative approaches to MDA. Studies involved four intervention years, with final evaluation in the fifth year. Mass drug administration given annually or twice over 4 years reduced average prevalence and intensity of schistosome infections, but not all villages that were treated in the same way responded similarly. There are multiple ways by which responsiveness to MDA, or the lack thereof, could be measured. In the analyses presented here, we defined persistent hotspots (PHS) as villages that achieved less than 35% reduction in prevalence and/or less than 50% reduction in infection intensity after 4 years of either school-based or community-wide MDA, either annually or twice in 4 years. By this definition, at least 30% of villages in each of the five studies were PHSs. We found no consistent relationship between PHSs and the type or frequency of intervention, adequacy of reported MDA coverage, and prevalence or intensity of infection at baseline. New research is warranted to identify PHSs after just one or a few rounds of MDA, and new adaptive strategies need to be advanced and validated for turning PHSs into responder villages.

Cystic echinococcosis (CE) is a chronic, complex, and overlooked zoonotic disease caused by Echinococcus granulosus. In humans, it may result in a wide spectrum of clinical manifestations depending on the type of complications, ranging from asymptomatic infection to fatal disease. The primary complications and risk factors associated with CE are not well defined. We performed a retrospective, observational study of inpatients diagnosed with CE from January 1998 to December 2017 in the public health-care system of western Spain. Five hundred and six cases were analyzed. More than half of the patients (302 [59.7%]) were asymptomatic, and the diagnoses were made incidentally. A total of 204 (40.3%) patients had complications associated with CE; 97 (47.5%) were mechanical, 62 (30.4%) were infectious, 15 (7.3%) were immunoallergic, and 30 (14.7%) involved a combination of complications. Mortality was higher in patients with mechanical complications (9.4%) than in patients with infectious complications (5.6%) and in patients with allergic complications (0%) (odds ratio = 19.7, 95% CI, 4.3–89.1, P < 0.001). In summary, CE frequently results in complications, especially in the liver in younger patients and, regardless of other variables, such as size or stage of cyst. Mechanical problems and superinfection are the most frequent complications. CE is an obligatory diagnosis in patients with urticarial or anaphylactoid reactions of unknown cause in endemic areas.

Children in the Peruvian Amazon Basin are at risk of soil-transmitted helminths (STH) infections. This study aimed to determine the prevalence of STH infection in children from a rural Amazonian community of Peru and to elucidate epidemiological risk factors associated with its perpetuation while on a school-based deworming program with mebendazole. Stool samples of children aged 2–14 years and their mothers were analyzed through direct smear analysis, Kato–Katz, spontaneous sedimentation in tube, Baermann’s method, and agar plate culture. A questionnaire was administered to collect epidemiological information of interest. Among 124 children, 25.8% had one or more STH. Individual prevalence rates were as follows: Ascaris lumbricoides, 16.1%; Strongyloides stercoralis, 10.5%; hookworm, 1.6%; and Trichuris trichiura, (1.6%). The prevalence of common STH (A. lumbricoides, T. trichiura, and hookworm) was higher among children aged 2–5 years than older children (31.6% versus 12.8%; P = 0.01). In terms of sanitation deficits, walking barefoot was significantly associated with STH infection (OR = 3.28; CI 95% = 1.11–12.07). Furthermore, STH-infected children more frequently had a mother who was concomitantly infected by STH than the non-STH–infected counterpart (36.4% versus 14.1%, P = 0.02). In conclusion, STH infection is highly prevalent in children from this Amazonian community despite routine deworming. Institutional health policies may include hygiene and sanitation improvements and screening/deworming of mothers to limit the dissemination of STH. Further studies are needed to address the social and epidemiological mechanics perpetuating these infections.

Mass deworming of school-aged children with anthelmintics has been recognized as an effective approach for reducing the burden of soil-transmitted helminth (STH) infections. However, the consequences of this intervention on nontargeted parasite populations sharing the same gastrointestinal niche are unclear. We conducted a cross-sectional survey among three primary schools in Sululta town, Ethiopia, to examine the association between students’ histories of deworming treatment in the past 6 months and the prevalence of cestode and protozoan infections. An interviewer-led questionnaire administered to parents provided information on sociodemographic factors, and deworming status was ascertained from school records. Stool samples were collected from 525 children for microscopic examination. The independent associations of “any cestode” (positive either for Hymenolepis nana or Taenia spp. eggs) and “any protozoan” (positive either for Giardia lamblia or Entamoeba histolytica/Entamoeba dispar) with history of deworming were examined using logistic regression. Overall, 25.9% of children were infected with at least one intestinal parasite of which H. nana was the most common. In multivariate analyses, deworming in the past 6 months was positively associated with increased odds of both “any protozoan” and “any cestode” infections; the latter reached statistical significance (AOR = 1.83, 95% CI: 0.69–4.86, P = 0.220, AOR = 3.82, 95% CI: 1.17–12.73, P = 0.029, respectively). If this observed association is causal, a greater understanding of interspecies interactions within the gastrointestinal niche may elucidate possible consequences of mass deworming treatments against STHs on coexisting nontargeted parasites.

The Awa indigenous people of Ecuador live in remote areas and were included in health programs only recently. The first screening for parasitic infections in the Awa communities was implemented in the context of community epidemiology. During the site visits in each community, the health-care staff collected the samples for stool microscopy and serology for Strongyloides. A total of 705 individuals consented for the study, representing 40% of the Awa population living in the targeted communities; 184 (26%) participants supplied a stool sample. Giardia intestinalis was found in about 11% of samples. Prevalence of Ascaris lumbricoides and Trichuris trichiura was 54.9% and 36.9%, respectively. No hookworm eggs were found. In addition, Strongyloides stercoralis larvae were found in eight individuals (4.3%), whereas serology was positive in 22.7% of the individuals tested. The community-based approach resulted in an impressive participation. There was a high prevalence of parasites associated with relevant morbidity.

Geophagy, the craving and purposive consumption of earth, is commonly reported during pregnancy. To date, most studies of geophagy have been cross-sectional and have not assessed its relationship with HIV infection. Therefore, to concurrently examine proposed etiologies of geophagy, a cohort of 371 women with mixed HIV status from Nyanza region, Kenya were recruited in late pregnancy and interviewed about pica at nine time points, through 21 months postpartum. Nutritional status (hemoglobin concentration and food insecurity), physical health (HIV infection and gastrointestinal distress), and psychosocial health (depression and perceived stress) were also repeatedly assessed. Prevalence of geophagy was greatest during pregnancy and decreased significantly postpartum. In a two-level hierarchical linear model, a one-unit increase in average hemoglobin (g/dL) was associated with a 35% decrease in the odds of geophagy. The adjusted odds ratios (CI) of geophagy were 3.98 (2.99, 5.29), 2.54 (1.13, 5.69), and 1.68 (1.15, 2.44) times higher if a woman was pregnant, reported diarrhea in the prior 24 hours, or was HIV positive, respectively. The adjusted odds ratio of geophagy was 1.61 (1.06, 2.45) times higher if a woman reported geophagy during childhood. Our results lend greatest plausibility to the protection hypothesis (i.e., that geophagy occurs in response to compromised immunity and/or infection). Given the high prevalence of geophagy, clinicians should regularly screen for the behavior and measure inflammatory biomarkers before treating geophagy with iron supplements, which can exacerbate some infections.

Nomadic pastoralists are among the world’s hardest-to-reach and least served populations. Pastoralist communities are difficult to capture in household surveys because of factors including their high degree of mobility over remote terrain, fluid domestic arrangements, and cultural barriers. Most surveys use census-based sampling frames which do not accurately capture the demographic and health parameters of nomadic populations. As a result, pastoralists are “invisible” in population data such as the Demographic and Health Surveys (DHS). By combining remote sensing and geospatial analysis, we developed a sampling strategy designed to capture the current distribution of nomadic populations. We then implemented this sampling frame to survey a population of mobile pastoralists in southwest Ethiopia, focusing on maternal and child health (MCH) indicators. Using standardized instruments from DHS questionnaires, we draw comparisons with regional and national data finding disparities with DHS data in core MCH indicators, including vaccination coverage, skilled birth attendance, and nutritional status. Our field validation demonstrates that this method is a logistically feasible alternative to conventional sampling frames and may be used at the population level. Geospatial sampling methods provide cost-affordable and logistically feasible strategies for sampling mobile populations, a crucial first step toward reaching these groups with health services.

In low-resource settings, many children are severely ill at arrival to hospital. The risk factors for mortality among such ill children are not well-known. Understanding which of these patients are at the highest risk could assist in the allocation of limited resources to where they are most needed. A cohort study of severely ill children treated in the resuscitation room of the pediatric emergency department at Queen Elizabeth Central Hospital in Malawi was conducted over a 6-month period in 2017. Data on signs and symptoms, vital signs, blood glucose levels, and nutritional status were collected and linked with in-hospital mortality data. The factors associated with in-hospital mortality were analyzed using multivariable logistic regression. Data for 1,359 patients were analyzed and 118 (8.7%) patients died. The following factors were associated with mortality: presence of any severely deranged vital sign, unadjusted odds ratio (UOR) 2.6 (95% CI 1.7–4.0) and adjusted odds ratio (AOR) 3.2 (95% CI 2.0–5.0); severe dehydration, UOR 2.6 (1.4–5.1) and AOR 2.8 (1.3–6.0); hypoglycemia glycemia (< 5 mmol/L), UOR 3.6 (2.2–5.8) and AOR 2.7 (1.6–4.7); and severe acute malnutrition, UOR 5.8 (3.5–9.6) and AOR 5.7 (3.3–10.0). This study suggests that among severely sick children, increased attention should be given to those with hypo/low glycemia, deranged vital signs, malnutrition, and severe dehydration to avert mortality among these high-risk patients.

A chronic kidney disease of unknown etiology (CKDu) has been killing workers in Central America. Occupational heat stress is thought to play an important role. Leptospirosis and hantavirus have been suggested as additional possible risk factors. In a case–control study in a Nicaraguan mining community, a structured survey was administered to adults, and biological measurements and specimens were taken. Serum was analyzed for antibodies to Leptospira and hantavirus. Before statistical analysis, a board-certified nephrologist determined final case and control status based on serum creatinine and other laboratory values. Multivariable analysis was by logistic regression. In sensitivity analyses, cases were restricted to those diagnosed with CKDu in the previous 3 years. Of 320 eligible participants, 112 were classified as presumptive cases, 176 as controls and 32 as indeterminant. The risk of CKDu in those ever having worked in mining or construction was 4.4 times higher than in other participants (odds ratio = 4.44, 95% CI: 1.96–10.0, P = 0.0003). Eighty-three (26%) of the 320 participants were seropositive for at least one tested strain of Leptospira. No evidence of a causal link between leptospirosis or hantavirus and CKDu was found. The sensitivity analyses provide some evidence against the hypotheses that leptospirosis or hantavirus leads to CKDu within a few years. A major limitation was the impossibility of determining the absolute or relative timing of infection and CKDu onset. A prospective cohort design, with repeated collection of specimens over several years, could yield clearer answers about infections as potential etiologic agents in CKDu.

To explore the educational practices of antenatal care providers toward pregnant women with sickle cell disease (SCD) and sickle cell trait (SCT), a survey was conducted among selected doctors and midwives who provide antenatal care at the outpatient clinic of the Obstetric Department of the Korle-Bu Teaching Hospital, Accra, Ghana. The study explored their practices of screening for and patient education about SCD and SCT. Of the 102 respondents, 100(98%) stated that they were knowledgeable in the medical and genetic aspects of the disease. Regarding screening, 82(80.4%) reported mandatory screening for SCD, 9(8.8%) did not offer screening as routine, and 11(10.8%) gave patients the choice. The majority (93.1%) always informed patients when the test was positive but health-care providers less than six years experience were less likely to communicate SCT status to patients without the trait (odds ratio [OR] = 0.41, 95% CI [0.18–0.93]). Nurses/midwives were less likely to tell patients their carrier status (OR = 0.25, 95% CI [0.10–0.59]). There was also variation in referral practices for genetic counseling, with 26.5% always referring, 28.4% never doing so, and 45.1% only referring if the patient had questions. This may affect patients’ awareness of this genetic condition. Therefore, continuous medical education on SCD/SCT and standardization of counseling may help inform couples’ family planning choices and reduce the burden of the disease on future generation and health care.

Lower respiratory tract infections (LRTIs) are the leading cause of deaths in children < 5 years old worldwide, particularly affecting low-resource settings such as Aweil, South Sudan. In these settings, diagnosis can be difficult because of either lack of access to radiography or clinical algorithms that overtreat children with antibiotics who only have viral LRTIs. Point-of-care ultrasound (POCUS) has been applied to LRTIs, but not by nonphysician clinicians, and with limited data from low-resource settings. Our goal was to examine the feasibility of training the mid-level provider cadre clinical officers (COs) in a Médecins Sans Frontières project in South Sudan to perform a POCUS algorithm to differentiate among causes of LRTI. Six COs underwent POCUS training, and each subsequently performed 60 lung POCUS studies on hospitalized pediatric patients < 5 years old with criteria for pneumonia. Two blinded experts, with a tiebreaker expert adjudicating discordant results, served as a reference standard to calculate test performance characteristics, assessed image quality and CO interpretation. The COs performed 360 studies. Reviewers rated 99.1% of the images acceptable and 86.0% CO interpretations appropriate. The inter-rater agreement (κ) between COs and experts for lung consolidation with air bronchograms was 0.73 (0.63–0.82) and for viral LRTI/bronchiolitis was 0.81 (0.74–0.87). It is feasible to train COs in South Sudan to use a POCUS algorithm to diagnose pneumonia and other pulmonary diseases in children < 5 years old.

There is insufficient evidence on whether dengue rapid diagnostic tests (dRDTs) influence clinical decisions in endemic areas. Therefore, our objective was to evaluate the impact of dRDTs on the prescription of antibiotics and anti-inflammatory drugs by physicians in a dengue-endemic area in Colombia. A retrospective cohort study was conducted with 330 patients in Cali, Colombia, between January 2012 and December 2017. The exposure was defined by the result of the dRDT. The outcomes were prescription of antibiotics and anti-inflammatory drugs after results of dRDT. Incidence and RR with 95% CIs were estimated. Multivariate logistic regression models were fitted separately for each outcome. Antibiotics were prescribed in 3% exposed and 14% unexposed. Anti-inflammatory drugs were prescribed in 1.2% exposed and 7.9% unexposed. A positive dRDT reduced the prescription of anti-inflammatories (AdjOR: 0.06, 95% CI: 0.008–0.5) but, by itself, had no effect on antibiotics (AdjOR: 1.1, 95% CI: 0.2–6); however, in hospitalized patients, a positive result reduced the probability of antibiotic prescription (AdjOR: 0.02, 95% CI: 0.00–0.8). Despite limitations of current dRDTs, they influence treatment decisions. Further studies are needed to assess the effect of dRDTs in patient outcomes and health-care costs.

A 43-year-old man was admitted to the intensive care unit and diagnosed with yellow fever. He presented with refractory bleeding, extreme hyperferritinemia, and multiple organ dysfunction syndrome, requiring renal replacement therapy, mechanical ventilation, and treatment with vasoactive drugs. Because the bleeding did not respond to fresh-frozen plasma administration, the patient received therapeutic plasma exchange, which was accompanied by a marked improvement of the clinical and biochemical parameters, including a significant decline in serum ferritin levels.

Zika virus (ZIKV) serological diagnostics are compromised in areas where dengue viruses (DENV) co-circulate because of their high levels of protein sequence homology. Here, we describe the characterization of a Zika blockade-of-binding ELISA (Zika BOB) and a Zika microneutralization assay (Zika MN) for the detection of ZIKV nonstructural protein 1 (NS1)–specific antibodies and ZIKV neutralizing antibodies, respectively. Zika BOB and Zika MN cutoffs were established as 10 and 100 endpoint titers, respectively, using samples collected pre- and post-virologically confirmed ZIKV infection from subjects living in DENV-endemic areas. Specificity of the assays was equally high, whereas sensitivity of Zika BOB was lower than that of Zika MN, especially in samples collected > 6 months post-infection. Immunosurveillance analysis, using combined results from both Zika BOB and Zika MN, carried out also in DENV-endemic regions in Colombia, Honduras, Mexico, and Puerto Rico before (2013–2014) and after (2017–2018) ZIKV introduction in the Americas suggests unapparent ZIKV seroprevalence rates ranged from 25% to 80% over the specified period of time in the regions investigated.