The American Journal of Tropical Medicine and Hygiene - Current Issue

Malaria chemoprophylaxis has become increasingly prominent now that it is used for vulnerable populations in endemic regions in addition to nonimmune travelers to those regions. The objective would be a drug with > 95% efficacy and that is easily tolerated, including in children and pregnant women. For individuals who prefer weekly rather than daily drug administration, a further objective is a product that is administered weekly. The deficiencies of present agents are parasite resistance to chloroquine, neuropsychiatric liability of mefloquine, the need for daily dosing for atovaquone–proguanil, and daily dosing plus adverse reactions for doxycycline. A primaquine analogue, tafenoquine, has a 17-day half-life and was approved for weekly prophylaxis in the United States and in Australia in 2018. Weekly tafenoquine was equal to mefloquine in efficacy in nonimmunes. The tafenoquine label contains a contraindication for preexisting psychosis, but not for the broad number of other neuropsychiatric disorders which are listed as contraindications in the mefloquine label. As an 8-aminoquinoline, tafenoquine is contraindicated for glucose-6-phosphate dehydrogenase (G6PD)-deficient persons or in pregnancy if the fetus might be G6PD deficient. Other possible significant adverse reactions for tafenoquine are declines in hemoglobin levels reported in some G6PD-normal patients, asymptomatic elevations in methemoglobin, and minor psychiatric events. The lack of broad neuropsychiatric adverse reactions suggests that tafenoquine may have a role as the weekly prophylactic of choice for G6PD-normal persons.

Strongyloides stercoralis, a worldwide-distributed soil-transmitted helminth, causes chronic infection which may be life threatening. Limitations of diagnostic tests and nonspecificity of symptoms have hampered the estimation of the global morbidity due to strongyloidiasis. This work aimed at assessing S. stercoralis–associated morbidity through a systematic review and meta-analysis of the available literature. MEDLINE, Embase, CENTRAL, LILACS, and trial registries (WHO portal) were searched. The study quality was assessed using the Newcastle–Ottawa scale. Odds ratios (ORs) of the association between symptoms and infection status and frequency of infection-associated symptoms were calculated. Six articles from five countries, including 6,014 individuals, were included in the meta-analysis—three were of low quality, one of high quality, and two of very high quality. Abdominal pain (OR 1.74 [CI 1.07–2.94]), diarrhea (OR 1.66 [CI 1.09–2.55]), and urticaria (OR 1.73 [CI 1.22–2.44]) were associated with infection. In 17 eligible studies, these symptoms were reported by a large proportion of the individuals with strongyloidiasis—abdominal pain by 53.1% individuals, diarrhea by 41.6%, and urticaria by 27.8%. After removing the low-quality studies, urticaria remained the only symptom significantly associated with S. stercoralis infection (OR 1.42 [CI 1.24–1.61]). Limitations of evidence included the low number and quality of studies. Our findings especially highlight the appalling knowledge gap about clinical manifestations of this common yet neglected soil-transmitted helminthiasis. Further studies focusing on morbidity and risk factors for dissemination and mortality due to strongyloidiasis are absolutely needed to quantify the burden of S. stercoralis infection and inform public health policies.

Brucellosis is an important but neglected zoonosis that causes serious economic losses both in livestock and human populations. The aim of the present study was to estimate the true prevalence of brucellosis together with diagnostic sensitivity and specificity of three serological tests in humans of the northwestern part of Ecuador using a Bayesian approach adjusted for the dependencies among the multiple tests to avoid any misinterpretation. In addition, the causal agent responsible for human brucellosis was also identified. Using a total of 3,733 samples collected from humans in this area between 2006 and 2008, the prevalence of human brucellosis and the diagnostic test characteristics of the Rose Bengal fast agglutination test (RBT), Wright’s slow agglutination test with ethylenediaminetetraacetic acid disodium salt dehydrate (EDTA) (SAT-EDTA), and indirect ELISA (iELISA) were estimated using a Bayesian approach. The estimated true prevalence of human brucellosis was 1% (credibility interval: 0.4–1.6). The sensitivities of iELISA and RBT were higher than and similar (95.1% and 95.0%, respectively) to those of SAT-EDTA (60.8%). Even though all tests indicated a high specificity (> 99.0%), the specificity of SAT-EDTA was highest (99.9%). The circulating strain in this study area was identified to be Brucella abortus biotype 4 based on culture and microbiological characterization. The RBT and the iELISA are recommended for estimating the true prevalence of human brucellosis and/or for surveillance programs following their high sensitivities and specificities. The proposed strategy supports evidence-based medicine for clinicians and policy-makers to ensure appropriate preventive and control program of brucellosis worldwide.

The present study aimed to detect Bartonella DNA in cats belonging to shelters, and to evaluate risk factors, clinical signs, and hematological abnormalities associated with infection. Complete blood counts and screening for the presence of Bartonella DNA were performed on cats’ ethylenediamine tetraacetic acid anticoagulant–blood samples. Eighty-three cats (39.9%) were positive for Bartonella species. Bartonella DNA was also detected in fleas and in the blood of cats infested by positive flea. Cats that had not been sterilized, had outdoor access, had histories of fights, and had concurrent flea infestation were more likely to be infected by Bartonella species (P < 0.05). Age and sex were not associated with infection. Fifty-one (38.6%) symptomatic cats were positive to Bartonella species (P > 0.05). Clinical conditions most commonly observed were signs of respiratory abnormality and Sporothrix species coinfection (P > 0.05). Regarding hematological changes, eosinophilia was associated with infection (P < 0.05). A high frequency of Bartonella species infection was found in shelter cats and highlights the importance of adequate flea-control programs to prevent infection in cats and consequently in adopters and other animals.

The diarrheal disease “cholera” is caused by Vibrio cholerae, and is primarily confined to endemic regions, mostly in Africa and Asia. It is punctuated by outbreaks and creates severe challenges to public health. The disease-causing strains are most-often members of serogroups O1 and O139. PCR-based methods allow rapid diagnosis of these pathogens, including the identification of their biotypes. However, this necessitates the selection of specific target sequences to differentiate even the closely related biotypes of V. cholerae. Oligonucleotides for selective amplification of small RNA (sRNA) genes that are specific to these V. cholerae subtypes were designed. The resulting multiplex PCR assay was validated using V. cholerae cultures (i.e., 19 V. cholerae and 22 non–V. cholerae isolates) and spiked stool samples. The validation using V. cholerae cultures and spiked stool suspensions revealed detection limits of 10–100 pg DNA per reaction and 1.5 cells/mL suspension, respectively. The multiplex PCR assay that targets sRNA genes for amplification enables the sensitive and specific detection, as well as the differentiation of V. cholerae—O1 classical, O1 El Tor, and O139 biotypes. Most importantly, the assay enables fast and cheaper diagnosis compared with classic culture-based methods.

In August 2015, an outbreak of cholera was reported in Tanzania. In cholera-affected areas of urban Dar es Salaam and Morogoro, many households obtained drinking water from vendors, who sold water from tanks ranging in volume from 1,000 to 20,000 L. Water supplied by vendors was not adequately chlorinated. The Tanzanian Ministry of Health, Community Development, Gender, Elderly and Children and the U.N. Children’s Fund, Tanzania, collaborated to enroll and train vendors to treat their water with 8.68-g sodium dichloroisocyanurate tablets (Medentech, Ireland). The Centers for Disease Control and Prevention (CDC) provided monitoring and evaluation support. Vendors were provided a 3-month supply of chlorine tablets. A baseline assessment and routine monitoring were conducted by ward environmental health officers. Approximately 3 months after chlorine tablet distribution, an evaluation of the program was conducted. The evaluation included a full enumeration of all vendors, an in-depth survey with half of the vendors enumerated, and focus group discussions. In total, 797 (88.9%) vendors were included in the full enumeration and 392 in the in-depth survey. Free residual chlorine (FRC) was detected in 12.0% of tanks at baseline and 69.6% of tanks during the evaluation; however, only 17.4% of these tanks had FRC ≥ 0.5 mg/L. The results suggest high acceptability and use of the chlorine tablets by water vendors. However, given variation in the water source used and longer storage times, dosing could be increased in future programming. Bulk chlorination using chlorine tablets offers an efficient community-level approach to treating water closer to the point of use.

Although vaccination is effective in preventing infection, pertussis remains endemic worldwide, including China. To lead better targeted prevention strategies, we examined dynamics of spatial and temporal patterns of pertussis transmission in Shandong, China, from 2009 to 2017. We used space-time cluster analysis, logistic regression analysis, and regression tree model to detect the changes in spatial patterns of pertussis infections in Shandong Province, China, between periods (2009–2011, 2012–2014, and 2015–2017). The yearly pertussis incidence rates dramatically increased by 16.8 times from 2009 to 2017. Shifting patterns of peaks of pertussis infections were observed over both time (from June–July to August–September) and space (from Linyi to Jinan), with increasing RR from 4.1 (95% CI: 2.3–7.4) (2009–2011) to 6.1 (95% CI: 5.6–6.7) (2015–2017) and obvious coincidence of peak time. West Shandong had larger odds of increased infections over the study period (odds ratio: 1.52 [95% CI: 1.05–2.17]), and pertussis had larger odds of spreading to east (odds ratio: 2.32 [95% CI: 1.63–3.31]) and north (odds ratio: 1.69 [95% CI: 1.06–2.99]) over time. Regression tree model indicated that the mean difference in yearly average pertussis incidence between 2009–2011 and 2015–2017 increased by more than 4-fold when the longitudes of counties are < 118.0°E. The geographic expansion of pertussis infection may increase the risk of epidemic peaks, coinciding with increased infections in the future. The findings might offer evidence for targeting preventive measures to the areas most in need to minimize the impact of the disease.

The diffusion of extended-spectrum beta-lactamase (E-ESBL)–producing Enterobacteriaceae is a major concern worldwide, especially in low-income countries, where they may lead to therapeutic failures. In hospitals, where colonization is the highest, E-ESBL transmission is poorly understood, limiting the possibility of establishing effective control measures. We assessed E-ESBL–acquisition routes in a neonatalogy ward in Madagascar. Individuals from a neonatology ward were longitudinally followed-up (August 2014–March 2015). Newborns’ family members’ and health-care workers (HCWs) were stool-sampled and tested for E-ESBL colonization weekly. Several hypothetical acquisition routes of newborns—e.g. direct contact with family members and HCWs and indirect contact with other newborns through environmental contamination, colonization pressure, or transient hand carriage—were examined and compared using mathematical modeling and Bayesian inference. In our results, high E-ESBL acquisition rates were found, reaching > 70% for newborns, > 55% for family members, and > 75% for HCWs. Modeling analyses indicated transmission sources for newborn colonization to be species dependent. Health-care workers’ route were selected for Klebsiella pneumoniae and Escherichia coli, with respective estimated transmission strengths of 0.05 (0.008; 0.14) and 0.008 (0.001; 0.021) ind−1 day−1. Indirect transmissions associated with ward prevalence, e.g. through hand carriage or environment, were selected for Enterobacter cloacae, E. coli, and K. pneumoniae (range 0.27–0.41 ind−1 day−1). Importantly, family members were not identified as transmission source. To conclude, E-ESBL acquisition sources are strongly species dependent. Escherichia coli and E. cloacae involve more indirect contamination, whereas K. pneumoniae also spreads through contact with colonized HCWs. These findings should help improve control measures to reduce in-hospital transmission.

Antibiotic resistance in pathogenic bacteria is a serious public health issue. The growing threat is a cause for concern and action to prevent the emergence of new resistant strains and the spread of existing ones to humans via the environment. This study aimed at identifying fecal pathogens in drinking water obtained from rural Andean households from Cajamarca, Peru, and measuring the antibiotic resistance profile of Escherichia coli. The study was embedded within a community-randomized controlled trial among 102 communities in the northern highlands of the Cajamarca region, Peru. Of 314 samples, 55.4% (95% CI [49.7, 61.0], n = 174) were identified as thermotolerant coliforms. Among the samples positive for thermotolerant coliform, E. coli was isolated in 37.3% (n = 117), Klebsiella spp. in 8.0% (n = 25), Enterobacter spp. in 5.1% (n = 16), and Citrobacter spp. in 2.5% (n = 8). Of the 117 E. coli samples, 48.7% (95% CI [39.4, 58.1], n = 57) showed resistance to any antibiotic. The E. coli antibiotic resistance profile showed highest resistance against tetracycline (37.6%), ampicillin (34.2%), sulfamethoxazole–trimethoprim (21.4%), and nalidixic acid (13%). Some 19.7% (95% CI [12.9, 28.0], n = 23) of the E. coli isolates displayed multidrug resistance, defined as resistance to at least three classes of antibiotics. The CTX-M-3 gene, which encodes extended-spectrum resistance to beta-lactamase antibiotics, was found in one isolate. The high prevalence of fecal contamination in drinking water highlights the importance of household water treatment methods. Likewise, the high levels of antibiotic resistance found indicate a need for further research to identify the origins of potential environmental contamination, misuse, or inadequate disposal of antibiotics.

Surface waters are an unappreciated reservoir of antimicrobial resistance (AMR). Poor sanitation brings different species of environmental bacteria into contact, facilitating horizontal gene transfer. To investigate the role of surface waters as potential reservoirs of AMR, we studied the point prevalence of fecal contamination, AMR genes, and Enterobacteriaceae in an urban lake and rural river system in Northeast Brazil in comparison with a lake and sewer system in Northeast Ohio in the United States. Surface water samples were examined for evidence of human fecal contamination using microbial source tracking and screened for plasmid-mediated fluoroquinolone resistance and carbapenemase genes. Enterobacteriaceae were detected using selective agar followed by antimicrobial susceptibility testing and detection of AMR genes by microarray, and classified by repetitive sequence–based polymerase chain reaction and multilocus sequence typing. Concentrations of human fecal bacteria in the Brazilian urban lake and sewage in Northeast Ohio were similarly high. Filtered water samples from the Brazilian urban lake, however, showed the presence of bla OXA-48, bla KPC, bla VIM-2, qnrS, and aac(6′)-lb-cr, whereas only bla VIM-2 was identified in raw sewage from Northeast Ohio. From the Brazilian urban lake, 85% of the Enterobacteriaceae (n = 40) cultured were resistant to at least one clinically important antibiotic, including ST131 Escherichia coli harboring the extended-spectrum beta-lactamase CTX-M. Although two isolates demonstrated polymyxin resistance, mcr-1/2 was not detected. Our findings indicate that surface waters in an urban Brazilian site can serve as an environmental reservoir of AMR and that improving wastewater treatment and sanitation generally may ameliorate AMR dissemination.

Knowledge and practices of rural South African populations with regard to antibiotic access and use (ABACUS) remain understudied. By using the case of four villages in the north east of the country, our aim was to investigate popular notions and social practices related to antibiotics to inform patient-level social interventions for appropriate antibiotic use. To achieve this, we investigated where community members (village residents) were accessing and sourcing medication, and what they understood antibiotics and antibiotic resistance (ABR) to be. Embedded within the multicountry ABACUS project, this qualitative study uses interviews and focus group discussions. A sample of 60 community members was recruited from the Agincourt Health and Demographic Surveillance System, situated in Mpumalanga Province, from April to August, 2017. We used the five abilities of seek, reach, pay, perceive, and engage in access to healthcare as proposed by Levesque’s “Access to Healthcare” framework. Respondents reported accessing antibiotics prescribed from legal sources: by nurses at the government primary healthcare clinics or by private doctors dispensed by private pharmacists. No account of the illegal purchasing of antibiotics was described. There was a mix of people who finished their prescription according to the instructions and those who did not. Some people kept antibiotics for future episodes of infection. The concept of “ABR” was understood by some community members when translated into related Xitsonga words because of knowledge tuberculosis and HIV/AIDS treatment regimens. Our findings indicate that regulation around the sale of antibiotics is enforced. Safer use of antibiotics and why resistance is necessary to understand need to be instilled. Therefore, context-specific educational campaigns, drawing on people’s understandings of antibiotics and informed by the experiences of other diseases, may be an important and deployable means of promoting the safe use of antibiotics.

Rickettsia and Leptospira spp. are under-recognized causes of acute febrile disease worldwide. Rickettsia species are often placed into the spotted fever group rickettsiae (SFGR) and typhus group rickettsiae (TGR). We explored the antibody prevalence among humans for these two groups of rickettsiae in four regions of Peru (Lima, Cusco, Puerto Maldonado, and Tumbes) and for Leptospira spp. in Puerto Maldonado and Tumbes. We also assessed risk factors for seropositivity and collected serum samples and ectoparasites from peri-domestic animals from households in sites with high human seroprevalence. In total, we tested 2,165 human sera for antibodies (IgG) against SFGR and TGR by ELISA and for antibodies against Leptospira by a microscopic agglutination test. Overall, human antibody prevalence across the four sites was 10.6% for SFGR (ranging from 6.2% to 14.0%, highest in Tumbes) and 3.3% for TGR (ranging from 2.6% to 6.4%, highest in Puerto Maldonado). Factors associated with seroreactivity against SFGR were male gender, older age, contact with backyard birds, and working in agriculture or with livestock. However, exposure to any kind of animal within the household decreased the odds ratio by half. Age was the only variable associated with higher TGR seroprevalence. The prevalence of Leptospira was 11.3% in Puerto Maldonado and 5.8% in Tumbes, with a borderline association with keeping animals in the household. We tested animal sera for Leptospira and conducted polymerase chain reaction (PCR) to detect Rickettsia species among ectoparasites collected from domestic animals in 63 households of seropositive participants and controls. We did not find any association between animal infection and human serostatus.

Lymph node tuberculosis (LNTB) is characterized by the enhanced baseline and antigen-specific production of type 1/17 cytokines and reduced baseline and antigen-specific production of interleukin (IL)-1β and IL-18 at the site of infection when compared with peripheral blood. However, the cytokine profile in the lymph nodes (LNs) of Mycobacterium tuberculosis culture–positive LNTB (LNTB+) and negative LNTB (LNTB−) has not been examined. To address this, we have examined the baseline and mycobacterial antigen–stimulated cytokine levels of type 1 (interferon gamma [IFNγ], tumor necrosis factor alpha [TNFα], IL-2), type 2 (IL-4, IL-5, and IL-13), type 17 (IL-17A, IL-17F, and IL-22), pro-inflammatory (IL-1α, IL-1β, IL-18, and granulocyte macrophage colony-stimulating factor [GM-CSF]), and regulatory cytokines (IL-10, transforming growth factor beta [TGF-β]) cytokines in the LN culture supernatants of LNTB+ and LNTB− individuals. We have observed significantly enhanced baseline levels of IL-13 and IL-10 and significantly reduced baseline levels of IL-4 and GM-CSF in LNTB+ individuals compared with LNTB− individuals. By contrast, we have observed significantly enhanced levels of type 1 (IFNγ, TNFα, and IL-2), type 17 (IL-17F and IL-22), and pro-inflammatory (IL-1α and GM-CSF) cytokines and significantly reduced levels of TGFβ in response to purified protein derivative, early secreted antigen-6, and culture filtrate protein-10 antigens in LNTB+ compared with LNTB− individuals. On phorbol 12-myristate 13-acetate/ionomycin stimulation, no significant difference was observed for any of the cytokines examined. Thus, our study revealed several interesting differences in the cytokine profiles of mycobacterial antigen–stimulated LN cultures in LNTB+ and LNTB− individuals. Therefore, we suggest the presence of mycobacteria plays a significant role in driving the cytokine response at the site of infection in LNTB.

In recent years, bed bugs have reappeared in greater numbers, more frequently, and are biting humans in many new geographic areas. Infestations by these hematophagous insects are rapidly increasing worldwide. Borrelia recurrentis, a spirochete bacterium, is the etiologic agent of louse-borne relapsing fever. The known vectors are body lice, Pediculus humanus humanus. However, previous studies have suggested that bed bugs might also be able to transmit this bacterium. Adult Cimex lectularius were artificially infected with a blood meal mixed with bacterial suspension of B. recurrentis. They were subsequently fed with pathogen-free human blood until the end of the experiment. Bed bugs and feces were collected every 5 days to evaluate the capacity of bed bugs to acquire and excrete viable B. recurrentis using molecular biology, cultures, fluorescein diacetate and immunofluorescence assays. The feces collected on the day 5 and 10 postinfection contained viable bacteria. Immunofluorescence analysis of exposed bed bugs showed the presence of B. recurrentis in the digestive tract, even in bed bugs collected on day 20 after infection. Like human body lice, bed bugs can acquire, maintain, and excrete viable B. recurrentis that might infect humans through skin lesions. This preliminary work suggests that bed bugs might be competent vectors of B. recurrentis. Because bed bugs and body lice may share the same ecological niches, the role of bed bugs in transmitting recurrent fevers deserves further study.

Puerto Rico was severely impacted by Hurricanes Irma and Maria in September 2017. The island has been endemic for dengue viruses (DENV) and recently suffered epidemics of chikungunya (CHIKV 2014) and Zika (ZIKV 2016) viruses. Although severe storms tend to increase the number of vector and nuisance mosquitoes, we do not know how they influence Aedes aegypti populations and arboviral transmission. We compared the abundance of female Ae. aegypti in autocidal gravid ovitraps (AGO traps), container habitats, and presence of RNA of DENV, CHIKV, and ZIKV in this vector before and after the hurricanes in Caguas city and in four communities in southern Puerto Rico. Two of these communities were under vector control using mass AGO trapping and the other two nearby communities were not. We also investigated mosquito species composition and relative abundance (females/trap) using Biogents traps (BG-2 traps) in 59 sites in metropolitan San Juan city after the hurricanes. Mosquitoes sharply increased 5 weeks after Hurricane Maria. Ensuing abundance of Ae. aegypti was higher in Caguas and in one of the southern communities without vector control. Aedes aegypti did not significantly change in the two areas with vector control. The most abundant mosquitoes among the 26 species identified in San Juan were Culex (Melanoconion) spp., Culex quinquefasciatus, Culex nigripalpus, and Ae. aegypti. No arboviruses were detected in Ae. aegypti following the hurricanes, in contrast with observations from the previous year, so that the potential for Aedes-borne arboviral outbreaks following the storms in 2017 was low.

Anopheles jeyporiensis and Anopheles nivipes appear to play an important role in contemporary malaria transmission in Bangladesh. However, very little is known about the natural host selection of these vectors. Therefore, host selection of these two species was investigated in Bandarban, the most malarious region of Bangladesh. A total of 480 engorged mosquitoes were analyzed. The human blood index (HBI) of An. jeyporiensis varied from 4.17% in outdoor to 19.17% in indoor collections. Similarly, HBI of An. nivipes ranged between 0.83% and 22.50% from outdoor to indoor. For both species, cow blood indices were significantly higher than HBI in both indoor and outdoor collections. These data demonstrate the opportunistic and zoophilic nature of An. jeyporiensis and An. nivipes, which suggests that approaches such as zooprophylasis may prove beneficial as a control strategy.

Distributing long-lasting insecticidal nets (LLINs) to individuals living in malaria-endemic regions is a cornerstone of global malaria control. National malaria control programs aim to achieve “universal coverage” of at-risk populations to reach LLINs’ full potential to reduce malaria, progress of which is then measured by indicators constructed from standardized questionnaires. Through an exploration of variability in LLIN use in Cambodia, we argue that indicators of universal coverage of LLINs are not sufficiently commensurate with the realities they are intended to measure, limiting the suitability of the data to serve program and policy purposes in a malaria elimination era. Reflecting on the various sources of variability in LLIN use, we apply and extend the concept of “appropriateness” as a third prong to the widely used “efficacy” and “effectiveness” criteria for evaluating LLINs as a tool for malaria prevention. Describing first the different dimensions of the intervention and the sociocultural context separately, we will further show how the variability underlying both is affected and induced by inappropriate aspects of the intervention and the measurements of its impact. We consider the gap between “net use” and the numerical representations of such local net use justifies further exploration of potential strategies to improve LLIN use in subgroups where persisting malaria transmission clusters.