The American Journal of Tropical Medicine and Hygiene - Volume 100, Issue 3, March 2019

A major earthquake in 2015 that struck Nepal created a favorable environment for the rapid spread of infectious diseases. In anticipation of a cholera outbreak in 2016, UNICEF, Johns Hopkins University, and the Group for Technical Assistance, Nepal, collaborated to assist the government of Nepal to strengthen early warning surveillance, laboratory-based diagnosis, and field investigation. This article outlines the challenges and lessons learned in cholera prevention and control based on the authors’ experiences in 2016. Priorities for the future plan should include sustaining the enhanced surveillance system for acute gastroenteritis and cholera, rolling out a rapid diagnostic test, and ensuring rapid and systematic epidemiological investigation and environmental testing.

Adults who have not grown up in a malaria-endemic area may experience severe malaria soon after entering a malarious area. Such mortality is usually limited to a short period of time (months), after which they are thought to be “immune.” Such anti-disease immunity may be more accurately considered as tolerance. Malaria rates of British soldiers during the Second World War reflected their time with suppressed infections and the transmission levels. Black workers from non-endemic areas on the Panama Canal experienced higher initial mortality and infection rates than co-located white workers for Plasmodium falciparum, whereas the known genetic resistance of blacks to Plasmodium vivax reversed these rates. The ethnic differences observed in malaria rates may have more to do with acquired tolerance than genetic resistance. Long-term (years) sub-patent infections may maintain host tolerance, and elimination of malaria infections may place these adults at subsequent risk of severe malaria.

Schistosoma japonicum is a digenetic blood fluke that has been implicated in the carcinogenesis of several human malignancies, notably liver and colorectal cancer (CRC). Schistosoma japonicum–associated colorectal cancer (SACC) is a distinct subtype with biological behavior analogous to colitis-induced CRC. The clinicopathological characteristics of SACC include young age at diagnosis, predominance among males, a strong predilection for the sigmoid colon and rectum, multifocal distribution, frequent mucinous histology, and poor prognosis. In addition to chronic inflammation, immunomodulation, and schistosomal toxins, bacterial coinfection appears to play an important role in the carcinogenic process. The present review provides the most recent updates on epidemiology, pathobiology, and clinical and prognostic features pertaining to SACC.

Rodents are the most prominent animal host of Bartonella spp., which are associated with an increasing number of human diseases worldwide. Many rodent species thrive in urban environments and live in close contact with people, which can lead to an increased human risk of infection from rodent-borne pathogens. In this study, we explored the prevalence and distribution of Bartonella spp. in rodents in urban, developing, and rural environments surrounding a growing city in Sarawak, Malaysian Borneo. We found that although Bartonella spp. infection was pervasive in most rodent species sampled, prevalence was highest in urban areas and infection was most commonly detected in the predominant indigenous rodent species sampled (Sundamys muelleri). Within the urban environment, parks and remnant green patches were significantly associated with the presence of both S. muelleri and Bartonella spp., indicating higher localized risk of infection for people using these environments for farming, foraging, or recreation.

Existing methodologies to record diarrheal disease incidence in households have limitations due to a high-episode recall error outside a 48-hour window. Our objective was to use mobile phones for reporting diarrheal episodes in households to provide real-time incidence data with minimum resource consumption and low recall error. From June 2014 to June 2015, we enrolled 417 low-income households in Dhaka, Bangladesh, and asked them to report diarrheal episodes to a call center. A team of data collectors then visited persons reporting the episode to collect data. In addition, each month, the team conducted in-home surveys on diarrhea incidence for a preceding 48-hour period. The mobile phone surveillance reported an incidence of 0.16 cases per person-year (95% CI: 0.13–0.19), with 117 reported diarrhea cases, and the routine in-home survey detected an incidence of 0.33 cases per person-year (95% CI: 0.18–0.60), the incidence rate ratio was 2.11 (95% CI: 1.08–3.78). During focus group discussions, participants reported a lack in motivation to report diarrhea by phone because of the absence of provision of intervening treatment following reporting. Mobile phone technology can provide a unique tool for real-time disease reporting. The phone surveillance in this study reported a lower incidence of diarrhea than an in-home survey, possibly because of the absence of intervention and, therefore, a perceived lack of incentive to report. However, this study reports the untapped potential of mobile phones in monitoring infectious disease incidence in a low-income setting.

Burkholderia pseudomallei, a bacterium that lives in the soil of the tropics, causes the disease melioidosis. This retrospective study investigated the temporospatial epidemiology of the 49 laboratory-confirmed melioidosis cases in the Torres Straits Islands of tropical Australia between 1997 and 2017. An identifiable risk factor for the disease was present in 43/49 (88%) cases and in 35/36 (97%) cases with complete clinical data. The mean incidence of melioidosis varied across the region, from 0/100,000 persons/year in the Eastern Island Cluster to 116.1/100,000 persons/year in the Near Western Island Cluster. An environmental suitability score for the growth of B. pseudomallei—constructed using the rainfall, vegetation, and soil type on each island—correlated with disease incidence (Spearman’s rho 0.51; P = 0.035). Melioidosis is an opportunistic disease that occurs in patients with specific risk factors, but its incidence is also strongly influenced by environmental factors that favor the growth of the causative organism.

Extended-spectrum β-lactamases (ESβLs) pose a serious problem in the treatment of urinary tract infections (UTIs). The ESβL-producing organism is an expanding global health problem. Therefore, screening for ESβL, detection of their drug-resistance pattern, and molecular characterization should be a continuous process. The present study was performed to determine the antibiotic resistance profile and the genetic characterization of ESβL isolates from hospital- and community-acquired UTIs. Two hundred fifty Enterobacteriaceae isolates were obtained from urine samples of outpatient clinic attendants and hospitalized patients at Kasr Al-Aini Hospital. By phenotypic screening tests, 100 ESβL isolates were detected among the studied groups. Furthermore, detection of beta-lactamase (bla) cefotaxime (CTX)-M, sulfhydryl variable, and temoneira ESβL genes was investigated by polymerase chain reaction. A subset of 25 CTX-M–positive isolates was further identified by gene sequencing technology. Among the 100 ESβL isolates, 66% were Escherichia coli and 34% were Klebsiella spp. There was no statistical difference in the prevalence of ESβL Enterobacteriaceae in community-acquired versus hospital-acquired UTIs. The susceptibility of all ESβL isolates to carbapenems was the most prevalent finding. In addition, all ESβL E. coli isolates were susceptible to fosfomycin, whereas all community-acquired ESβL isolates were susceptible to nitrofurantoin. A total of 98% of the ESβL isolates harbored bla-CTX-M genes, with CTX-M-15 being the most prevalent. It could be concluded that ESβL production is present at a high rate among Egyptian patients with hospital- and community-acquired UTI. The high prevalence of bla-CTX-M may suggest it as a candidate for molecular screening of ESβL.

Here we report the first incidence of New Delhi metallo-β-lactamase (NDM-1)–producing Acinetobacter baumannii in Peru, identified via a strain-based nosocomial surveillance project carried out in Lima and Iquitos. The bla NDM-1 gene was detected by multiplex polymerase chain reaction (PCR) and confirmed by loci sequencing. Acinetobacter baumannii is a nearly ubiquitous and promiscuous nosocomial pathogen, and the acquisition of bla NDM-1 by A. baumannii may facilitate an increase in the prevalence of this important resistance marker in other nosocomial pathogens.

Scrub typhus is caused by the intracellular bacterium Orientia tsutsugamushi. The 56-kDa type-specific antigen (TSA) displays a significant antigenic variation across different O. tsutsugamushi strains. To minimize the influence of the antigenic diversity of TSA on assay sensitivity, we developed a mixed-TSA enzyme-linked immunosorbent assay (mixed-TSA ELISA) using a mixture of recombinant TSAs of prototype (Karp, Gilliam, and Kato) and local (TW-1, TW-10, TW-19, and TW-22) O. tsutsugamushi strains as antigens to detect immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against O. tsutsugamushi. These four local strains covered a major part of the total genetic diversity of TSA gene of O. tsutsugamushi in Taiwan. A total of 109 acute-phase serum samples from O. tsutsugamushi polymerase chain reaction–positive, scrub typhus patients, and 82 negative control serum samples from non-scrub typhus cases were used for evaluation of the recombinant TSA-based ELISA. We compared the performance of the mixed-TSA ELISA with immunofluorescence assay (IFA), which is considered the gold standard method for the serological diagnosis of scrub typhus. The results indicated that the sensitivity of IgM mixed-TSA ELISA (80.7%) was significantly higher than that of IgM IFA (68.8%). We demonstrated that the mixed-TSA ELISA had a high sensitivity and specificity and can be used for screening of scrub typhus patient in the early phase of the disease.

Interferon-gamma release assays are increasingly used in children to establish evidence of tuberculosis (TB) infection and to assist in the diagnosis of TB disease. The QuantiFERON-TB Gold In-Tube assay is being phased out in favor of a next-generation test, the QuantiFERON-TB Gold Plus (QFT-Plus) assay. The QFT-Plus assay is designed with two antigen tubes to differentially stimulate CD4+ and CD8+ T cells. The performance of this assay has been documented extensively in adults but has not yet been evaluated in children. Here, we compare the performance of the two assays in a cohort of 46 children exposed to TB and 12 children diagnosed with TB disease in Eswatini. The tests demonstrated excellent concordance in both TB disease (100% agreement, Cohen’s kappa = 1) and TB infection (96% agreement, Cohen’s kappa = 0.91). Most of the children with household exposure tested negative for TB infection by both tests, indicating the ongoing need for new tests for TB infection that can be easily implemented in TB high-burden settings at minimal cost.

Anopheles mosquitoes vary in habitat preference, feeding pattern, and susceptibility to various measures of vector control. Consequently, it is important that we identify reservoirs of disease, identify vectors, and characterize feeding patterns to effectively implement targeted control measures. Using 467 anopheline mosquito abdomen squashes captured in Madagascar, we designed a novel ligase detection reaction and fluorescent microsphere assay, dubbed Bloodmeal Detection Assay for Regional Transmission (BLOODART), to query the bloodmeal content, identify five Anopheles mosquito species, and detect Plasmodium infection. Validation of mammalian bloodspots was achieved by preparation and analysis of known hosts (singular and mixed), sensitivity to degradation and storage method were assessed through mosquito feeding experiments, and quantification was explored by altering ratios of two mammal hosts. BLOODART identifications were validated by comparison with mosquito samples identified by sequenced portions of the internal transcribed spacer 2. BLOODART identification of control mammal bloodspots was 100% concordant for singular and mixed mammalian blood. BLOODART was able to detect hosts up to 42 hours after digestion when mosquito samples were stored in ethanol. A mammalian host was identified in every field-collected, blood-fed female Anopheles mosquito by BLOODART. The predominant mosquito host was cow (n = 451), followed by pig (n = 26) and human (n = 25). Mixed species bloodmeals were commonly observed (n = 33). A BLOODART molecular identification was successful for 318/467 mosquitoes, with an overall concordance of 60% with all field-captured, morphologically identified Anopheles specimens. BLOODART enables characterization of large samples and simultaneous pathogen detection to monitor and incriminate disease vectors in Madagascar.

Maternal infection during pregnancy can have lasting effects on neurodevelopment, but the impact of malaria in pregnancy on child neurodevelopment is unknown. We present a case of a 24-year-old gravida three woman enrolled at 14 weeks 6 days of gestation in a clinical trial evaluating malaria prevention strategies in pregnancy. She had two blood samples test positive for Plasmodium falciparum using loop-mediated isothermal amplification before 20 weeks of gestation. At 31 weeks 4 days of gestation, the woman presented with preterm premature rupture of membranes, and the twins were delivered by cesarean section. Twin A was 1,920 g and Twin B was 1,320 g. Both placentas tested negative for malaria by microscopy, but the placenta of Twin B had evidence of past malaria by histology. The twins’ development was assessed using the Bayley Scales of Infant and Toddler Development–Third Edition. At 1 year chronologic age, Twin B had lower scores across all domains (composite scores: cognitive, Twin A [100], Twin B [70]; motor, Twin A [88], Twin B [73]; language, Twin A [109], Twin B [86]). This effect persisted at 2 years chronologic age (composite scores: cognitive, Twin A [80], Twin B [60]; motor, Twin A [76], Twin B [67]; language, Twin A [77], Twin B [59]). Infant health was similar over the first 2 years of life. We report differences in neurodevelopmental outcomes in placental malaria-discordant dizygotic twins. Additional research is needed to evaluate the impact of placental malaria on neurodevelopmental complications. Trial registration number: ClinicalTrials.gov number, NCT02163447. Registered: June 2014, https://clinicaltrials.gov/ct2/show/NCT02163447.

Controlled human malaria infection (CHMI) is a powerful tool to evaluate the efficacy of malaria vaccines and pharmacologics. Investigators at the University of Maryland, Baltimore, Center for Vaccine Development (UMB-CVD) pioneered the technique in the 1970s and continue to advance the frontiers of CHMI research. We reviewed the records of 338 malaria-naive volunteers who underwent CHMI at UMB-CVD with Plasmodium falciparum from 1971 until 2017. These 338 volunteers underwent 387 CHMI events, including 60 via intradermal injection or direct venous inoculation (DVI) of purified, cryopreserved sporozoites. No volunteer suffered an unplanned hospitalization or required intravenous therapy related to CHMI. Median prepatency period was longer in challenges using NF54 (9 days) than in those using 7G8 (8 days), P = 0.0006 by the log-rank test. With dose optimization of DVI, the prepatent period did not differ between DVI and mosquito bite challenge (log-rank test, P = 0.66). Polymerase chain reaction (PCR) detected P. falciparum infection 3 days earlier than thick smears (P < 0.001), and diagnosis by ultrasensitive PCR was associated with less severe symptoms than smear-based diagnosis (39% versus 0%, P = 0.0003). Historical studies with NF54 showed a shorter median prepatency period of 10.3 days than more recent studies (median 11.0 days, P = 0.02) despite significantly lower salivary gland scores in earlier studies, P = 0.0001. The 47-year experience of CHMI at UMB-CVD has led to advancements in sporozoite delivery, diagnostics, and use of heterologous challenge. Additional studies on new challenge strains and genomic data to reflect regional heterogeneity will help advance the use of CHMI as supporting data for vaccine licensure.

Malaria is traditionally diagnosed by blood smear microscopy, which requires continuous resource-demanding training. In areas with only a few cases of malaria, a simple and rapid test that can reliably exclude malaria could significantly reduce the need for microscopy and training. We evaluated whether loop-mediated isothermal amplification (LAMP) for screening malaria parasites could reduce the workload in the diagnosis of malaria. Loop-mediated isothermal amplification was used to analyze 38 ethylene-diamine-tetraacetic acid (EDTA) blood samples from 23 patients who had previously been tested for malaria by microscopy, antigen-based rapid diagnostic test (antigen-RDT), and in-house real-time polymerase chain reaction (RT-PCR). The samples included blood with low-level parasitaemia and samples with discrepancies between the results of the different methods. Loop-mediated isothermal amplification detected malaria parasites in 27 of 28 samples that were positive according to in-house RT-PCR. There were negative microscopy results in 10 of these and negative antigen-RDT results in 11. The sample with a negative LAMP result and positive in-house RT-PCR result was from a patient who had recently been treated for low-level Plasmodium falciparum malaria parasitaemia. We found LAMP to be reliable for malaria screening and suitable for replacing microscopy without loss of performance. The low number of LAMP-positive samples needing microscopy can be handled by a limited number of trained microscopists. The time saved on training and documentation was estimated to be 520 working hours yearly in our laboratory. Using LAMP for primary screening of patient samples, we have made a diagnostic workflow that ensures more reliable, faster, and less resource-demanding diagnosis of malaria.

Gametocytes are sexual stage malaria parasites responsible for transmission to mosquitoes. Multiple gametocyte-producing clones may be present in natural infections, but the molecular characterization of gametocytes is challenging. Because of their magnetic properties, gametocyte enrichment can be achieved by magnetic fractionation. This increases detection sensitivity and allows specific genotyping of clones that contribute to malaria transmission. Here, we determined the percentage of Plasmodium falciparum gametocytes successfully bound to magnetic activated cell sorting (MACS) LS columns during magnetic fractionation and assessed whether columns can be reused without risking contamination or affecting column binding efficiency. Bound column fractions were quantified using multiplex quantitative reverse transcription polymerase chain reaction (qRT-PCR) for male (pfMGET) and female (CCp4) gametocytes and ring-stage asexual parasites (SBP1). To investigate cross contamination between columns, parasite strain identity was determined by merozoite surface protein 2 genotyping followed by capillary electrophoresis fragment sizing. A reproducible high percentage of gametocytes was bound to MACS LS columns with < 5% gametocytes appearing in the flow-through and < 0.6% asexual ring-stage parasites appearing in the gametocyte fraction. A high yield (> 94%) of gametocyte enrichment was achieved when columns were used up to five times with lower binding success after eight times (79%). We observed no evidence for cross contamination between columns.

Forty-five Schistosoma mansoni egg–negative/circulating cathodic antigen (CCA) low (Trace-1+) positive children in areas of very low prevalence were followed up daily for 30 days. Stool and urine specimens were collected and examined each day from each child. At the midpoint of the study, three egg-positive control persons with light intensity infection were included in the protocol. Stool samples were examined by the Kato–Katz (four slides/stool sample) technique and all S. mansoni egg–negative stools were further tested by the “miracidia hatching test” (MHT). Urine samples were examined by the point-of-care CCA assay (POC-CCA). Over 30 days, only one of 1,338 consecutive stool samples from study subjects was S. mansoni egg and MHT positive (0.07%). Egg counts fluctuated daily in stools from positive controls and S. mansoni miracidia were detected in all but two samples by the MHT. Point-of-care–circulating cathodic antigen bands were scored from G1 to G10 and then translated to standard Trace, 1+, 2+, 3+ banding patterns. In two districts, the POC-CCA assays were Trace or 1+ for both the study children and the positive controls. In the third district, the POC-CCA assays were Trace or 1+ for the study children and 1+ or 2+ for the positive control. We conclude that in areas with extremely low prevalence S. mansoni egg–negative and CCA-Trace or 1+ children are unlikely to pose substantial risks to continued transmission of schistosomiasis. In this setting, POC-CCA Trace or 1+ readings are likely to be false positives or perhaps represent low-level single-sex schistosome infections.

Mitochondrial genome analysis of Schistosoma japonicum suggests that diversity of intermediate host snails drove intra-species divergence during its expansion in Asia. We applied the knowledge of this genomic variation to study an unusual patient we recently diagnosed with schistosomiasis. The patient had not visited any schistosomiasis-endemic countries for more than 35 years and had no idea where she became infected. Unusual clinical features of this patient included the absence of egg granulomas in tissue and persistent noncalcified eggs despite multiple praziquantel (PZQ) treatments over 7 years. A digital droplet polymerase chair reaction (PCR) assay that specifically targets the schistosome 1,4 dihydronicotinamide adenine dinucleotide-1 (NADH1) dehydrogenase-1 mitochondrial gene successfully amplified parasite DNA extracted from colon biopsies. DNA sequence analysis of parasite DNA revealed that it was a Philippine strain of S. japonicum. Future molecular studies using stored DNA from patients such as this may provide new insight into why some persons do not respond well to PZQ treatment.

A 23-year-old recent emigrant from Afghanistan presented in August 2017 with severe wheezing and dyspnea that required hospital admission. Her illness was associated with marked peripheral blood eosinophilia (9,900–15,600/µL; 45.2–68%), as well as mild nausea, epigastric pain, and decreased appetite. She had lived until 3 months earlier in close proximity to cattle in her home in Kabul and did not recall eating watercress or other leafy plants associated with Fasciola hepatica transmission. Computerized tomography scanning showed bilateral ground-glass lung consolidations and multiple distinctive hypo-attenuating linear, tubuliform, and nodular liver lesions, including a large subcapsular hematoma. Numerous tests for rheumatological and malignant disorders were negative. Fasciola hepatica infestation was suspected on epidemiological, clinical, and radiographic grounds, and was confirmed by immunoblotting at the Centers for Disease Control (CDC). Multiple stool ova and parasite examinations were negative and endoscopic retrograde cholangiopancreatography did not identify trematodes. Her acute respiratory illness resolved with asthma-targeted therapies and her eosinophilia resolved with triclabendazole, which was obtained from CDC via an FDA Investigational New Drug application. Fascioliasis is uncommon in the United States, but the prolonged warfare and civil strife in Afghanistan and adjacent areas may lead to increased incidence outside the endemic region. Her case also demonstrates how hepatic imaging features of fascioliasis can be pathognomonic in clinical scenarios with eosinophilia and appropriate epidemiology and clinical features. We also highlight her relatively unusual presentation with symptoms of Loeffler-like syndrome alone.

Fascioliasis, caused by Fasciola hepatica and Fasciola gigantica infection, is a major food-borne trematodiasis in many places of the world, with the central region of Vietnam being reported as a highly endemic area. Stool examination for Fasciola eggs is not a sensitive method, and immunodiagnostic methods are preferable. We investigated various enzyme-linked immunosorbent assays (ELISAs) to evaluate their efficacy for fascioliasis diagnosis. Test sera used are primarily screened using an ELISA kit produced in Vietnam (VN kit; Viet Sinh Chemical Producing & Trading Co. Ltd., Ho Chi Minh City, Vietnam): Seropositive individuals having symptoms compatible with fascioliasis were regarded as clinically diagnosed fascioliasis cases. A commercial Fasciola IgG ELISA kit from Diagnostic Automation/Cortez Diagnostics, Inc. (USA kit; Woodland Hills, CA), which has been commonly used in Vietnam, was assessed and compared with in-house ELISA systems, including a cystatin-capture (CC) ELISA using crude worm extract (CWE) and an indirect ELISA using a synthetic peptide Ac-TPTCHWECQVGYNKTYDEE-NHMe designed from the F. gigantica cathepsin B (FgCB5) molecule. The USA kit was suitable for routine diagnosis after recalibration of the manufacturer’s suggested cutoff point. Cystatin-capture ELISA with CWE provided good sensitivity and specificity with perfect agreement to the results of the USA kit. In dot-blot ELISA, recombinant FgCB5 reacted more strongly with human antisera than did other F. gigantica antigens tested. Enzyme-linked immunosorbent assay using the synthetic peptide fragment of the FgCB5 exhibited nearly 80% sensitivity and specificity, but the test results showed low agreement with CC-ELISA or the USA kit. In conclusion, the commercially available Fasciola IgG ELISA kit from the United States and the in-house CC ELISA using CWE are suitable for practical diagnosis for fascioliasis.

Cholangiocarcinoma (CCA) is a cancer with high mortality owing to its aggressiveness and resistance to therapy. The liver flukes of the Opisthorchiidae family have been recognized as risk factors of CCA. Opisthorchis felineus infection occurs in Western Siberia, the biggest endemic area in the Russian Federation, and is associated with chronic inflammation of the bile ducts, which may be linked to severe hepatobiliary morbidity. We report two cases of confirmed CCA who had a chronic O. felineus infection. Both cases presented unspecific symptoms at the onset of the disease, a stage when severe pathological changes already had occurred. Both patients were living in endemic areas but did not receive any antihelminthic treatment. This report underlines the need for assessment of O. felineus infection as a causative factor of CCA. The results will provide further arguments for control of O. felineus in the Russian Federation.

The pig is the natural intermediate host of Taenia solium, a parasite causing significant burden of disease in both humans and pigs. Porcine cysticercosis is traditionally detected via tongue palpation and slaughterhouse meat inspection, both with limited sensitivity. Serum antibody detection has a better performance; however, it does not discriminate past from present infection. Serum antigen detection can demonstrate viable infection and gives a good estimate of parasitic load. This study evaluated a sandwich antigen-detection ELISA using monoclonal antibodies (MoAbs) 158C11 and 60H8 for the diagnosis of viable cysticercosis in pigs. Serum samples were used from 35 naturally T. solium cysticerci–infected pigs, 31 cysticercosis-negative pigs, and 22 pigs with Taenia hydatigena infection (to assess cross-reactions). Positive cysticercosis samples were subcategorized at necropsy according to parasitic burden as mild (1–10 viable cysts, n = 10), moderate (11–100 cysts, n = 5), or severe infection (more than 100 cysts, n = 20). This Ag-ELISA showed a sensitivity of 82.9% and a specificity of 96.8% when not considering cross-reactions with T. hydatigena. Hundred percentage of severely infected, 80% of moderately infected, and 50% of mildly T. solium–infected pigs tested positive. Twenty of 22 pigs with only T. hydatigena infections were positive, with 13 reaching saturating levels in the ELISA. The Ag-ELISA revealed the presence of live cysts and is, thus, a fairly reliable test to monitor experimental infection, response to treatment, and follow-up in animal models of cysticercosis. It should, however, be carefully interpreted when used in regions where T. hydatigena is endemic in pigs.

Manifestations of neurocysticercosis (NCC) are primarily due to host inflammatory responses directed at drug-damaged or naturally degenerating metacestodes (cysts) of the tapeworm Taenia solium. Prolonged high-dose corticosteroids are frequently required to control this inflammation in complicated disease, often causing severe side effects. Studies evaluating alternatives to corticosteroids are lacking. Here, we describe the clinical course of NCC in 16 patients prescribed etanercept (ETN), a tumor necrosis factor-alpha inhibitor to control inflammation resulting from anthelmintic treatment. Twelve patients with extraparenchymal NCC were administered ETN with corticosteroids (11/12, 91.7%) and/or methotrexate (9/12, 75.0%). The median age of the subgroup with extraparenchymal NCC was 40 years (range 26–57 years) and 66.7% were male. They were administered ETN for a median period of 311 days (range 31–461 days) and then followed for a median of 3.4 years (range 0.3–6.6 years). Among nine assessable patients, all improved clinically after starting ETN and one deteriorated transiently. Of the remaining three, one was lost to follow-up and two patients have improved but had not completed their assigned course. Four additional persons with recurrent perilesional edema (PE) episodes were given ETN for a median of 400.5 days (range 366–854 days) and followed post-ETN for a median of 1.7 years (range 0.2–2.4 years). All PE patients improved and two successfully tapered corticosteroids. Etanercept administration was associated with clinical improvement, stable disease, absence of recurrence, and lack of serious side effects. Etanercept appears to contribute to the control of inflammation and facilitate corticosteroid taper.

Cystic echinococcosis (CE) is a zoonosis caused by the larval stage of the tapeworm Echinococcus granulosus. In humans, the infection induces the formation of parasitic cysts mostly in the liver and lungs, but virtually any organ can be affected. CE of the bone is one of the rarest forms of the disease, yet it is also extremely debilitating for patients and hard to manage for clinicians. Unlike abdominal CE, there is currently no expert consensus on the management of bone CE. In this study, we conducted a survey of the clinical records of seven European referral centers for the management of patients with CE and retrieved data on the clinical management of 32 patients with a diagnosis of bone CE. Our survey confirmed that the patients endured chronic debilitating disease with a high rate of complications (84%). We also found that diagnostic approaches were highly heterogeneous. Surgery was extensively used to treat these patients, as well as albendazole, occasionally combined with praziquantel or nitaxozanide. Treatment was curative only for two patients, with one requiring amputation of the involved bone. Our survey highlights the need to conduct systematic studies on bone CE, both retrospectively and prospectively.

Acute undifferentiated febrile illness (AUFI) has been a diagnostic dilemma in the tropics. Without accurate point-of-care tests, information on local pathogens and clinical parameters is essential for presumptive diagnosis. A prospective hospital-based study was conducted at the Bangkok Hospital for Tropical Diseases from 2013 to 2015 to determine common etiologies of AUFI. A total of 397 adult AUFI cases, excluding malaria by blood smear, were enrolled. Rapid diagnostic tests for tropical infections were performed on admission, and acute and convalescent samples were tested to confirm the diagnosis. Etiologies could be identified in 271 (68.3%) cases. Dengue was the most common cause, with 157 cases (39.6%), followed by murine typhus (20 cases; 5.0%), leptospirosis (16 cases; 4.0%), influenza (14 cases; 3.5%), and bacteremia (six cases; 1.5%). Concurrent infection by at least two pathogens was reported in 37 cases (9.3%). Furthermore, characteristics of dengue and bacterial infections (including leptospirosis and rickettsioses) were compared to facilitate dengue triage, initiate early antibiotic treatment, and minimize unnecessary use of antibiotics. In conclusion, dengue was the most common pathogen for AUFI in urban Thailand. However, murine typhus and leptospirosis were not uncommon. Empirical antibiotic treatment using doxycycline or azithromycin might be more appropriate, but cost–benefit studies are required. Physicians should recognize common causes of AUFI in their localities and use clinical and laboratory clues for provisional diagnosis to provide appropriate treatment while awaiting laboratory confirmation.

We assessed carotid intima-media thickness (cIMT) and arterial stiffness in 28 children and adolescents with previous dengue hemorrhagic fever (DHF) (mean interval between DHF and cardiovascular assessment, 8.4 years), and 34 controls in a low-resource setting. Participants with previous DHF had an adjusted increased cIMT of 42.6 µm (95% confidence interval [CI]: 10.0–75.3, P = 0.01), and 61.7 µm (95% CI: 21.5–102.0, P < 0.01) in a subgroup analysis on dengue shock syndrome. There were no differences in arterial stiffness. In this first exploratory study, children and adolescents with a history of DHF had an increased cIMT, which may be modulated by dengue severity.

Scrub typhus (ST, Orientia tsutsugamushi), murine typhus (MT, Rickettsia typhi), and dengue virus (DENV) are important causes of childhood morbidity in Cambodia. This prospective, cross-sectional seroprevalence study determined the proportion of Cambodian children infected by these pathogens and the ages at which initial infection is likely to occur. A total of 993 patient serum samples were tested for MT- and ST-specific IgG, and 837 samples tested for DENV-specific IgG. Overall, ST, MT, and DENV seroprevalence was high, estimated at 4.2%, 5.3%, and 50.7%, respectively. Scrub typhus and MT seropositivity peaked in children aged 8–11 and 12–15 years, respectively, suggesting initial infection occurs in these ages. Dengue virus seroprevalence steadily increased with age, indicating constant DENV exposure. The results of this study suggest that in Cambodian children presenting with undifferentiated febrile illness, dengue should be considered high in the list of differential diagnoses, and empirical anti-rickettsial antimicrobial therapy may be more indicated in 8- to 15-year-olds.

Zika virus (ZIKV) has been presumed to be endemic in Southeast Asia (SEA), with a low rate of human infections. Although the first ZIKV evidence was obtained in the 1950s through serosurveys, the first laboratory-confirmed case was only detected in 2010 in Cambodia. The epidemiology of ZIKV in SEA remains uncertain because of the scarcity of available data. From 2016, subsequent to the large outbreaks in the Pacific and Latin America, several Asian countries started reporting increasing numbers of confirmed ZIKV patients, but no global epidemiological assessment is available to date. Here, with the aim of providing information on ZIKV circulation and population immunity, we conducted a seroprevalence study among blood donors in Vientiane, Laos. Sera from 359 asymptomatic consenting adult donors in 2003–2004 and 687 in 2015 were screened for anti-ZIKV IgG using NS1 ELISA assay (Euroimmun, Luebeck, Germany). Positive and equivocal samples were confirmed for anti-ZIKV–neutralizing antibodies by virus neutralization tests. Our findings suggest that ZIKV has been circulating in Vientiane over at least the last decade. Zika virus seroprevalence observed in the studied blood donors was low, 4.5% in 2003–2004 with an increase in 2015 to 9.9% (P = 0.002), possibly reflecting the increase of ZIKV incident cases reported over this period. We did not observe any significant difference in seroprevalence according to gender. With a low herd immunity in the Vientiane population, ZIKV represents a risk for future large-scale outbreaks. Implementation of a nationwide ZIKV surveillance network and epidemiological studies throughout the country is needed.

This study was conducted to find the burden of dengue virus (DENV) and Japanese encephalitis virus (JEV) among children under the age of 13, who presented with acute encephalitis syndrome at Mandalay Children Hospital in Myanmar in 2013. Molecular and serological investigations were performed on 123 cerebrospinal fluid (CSF) samples collected from these patients. By neutralization tests and/or virus isolation, four (3.3%) JEV- and one DENV-associated encephalitis cases (0.8%) were confirmed. Antibody titer against JEV Genotype 3 was the highest among the laboratory-confirmed JEV cases. One strain of DENV-1 with Genotype 1 was isolated from the CSF sample of the dengue encephalitis patient; this was similar to the virus circulating in the study area and neighboring countries. This study shows that flaviviruses are important pathogens causing encephalitis in Myanmar. Active disease surveillance, vector control, and vaccination programs should be enforced to reduce the morbidity and mortality caused by flavivirus encephalitis.

The largest epidemic of Lassa fever in recent history occurred in Nigeria in 2018. We assessed the potential for cases of Lassa fever originating in Nigeria to arrive at international destinations via air travel using a probabilistic model. We estimated no exported cases in 62% of 1,000 model simulations. In 30% of simulations, a single exported case was projected. Greater than 40% of outbound travelers from Nigeria arrived in the United States, the United Kingdom, and Ghana, placing these countries at greatest risk for receiving an exported case. There was a wide range in the capacity of highly connected countries to respond to infectious disease threats, as measured by the Infectious Disease Vulnerability Index. Although we quantified a low probability of case exportation during this outbreak, countries with the greatest connectivity to Nigeria should be alert to the potential risks of Lassa fever importation and be prepared to manage infected individuals.

This study aimed to assess baseline knowledge, attitudes, and practices about severe fever with thrombocytopenia syndrome (SFTS) and identify the target population for health education programs in endemic areas of Anhui, China. This cross-sectional study was conducted from May to June 2017. Of 752 participants, 383 (50.9%) were from Nanqiao District, 397 (52.8%) were female, and 430 (57.2%) were farmers; 37.4% had heard about SFTS, but knowledge of symptoms and signs including fever (34.2%), leukopenia (8.0%), and thrombocytopenia (10.1%) was low. Only 12.1% knew that SFTS virus is transmitted by ticks, 9.4% realized that the blood and body fluid of SFTS are infectious, and only 38.2% thought that the tick should be paralyzed using medical alcohol or iodine. Meanwhile, 61.3% wore long-sleeve clothes, whereas 20.2% used repellents. Median scores for knowledge, attitudes, and practices, and the total score were 4.0, 6.0, 5.0, and 16.0, respectively. Knowledge was influenced by region (OR = 0.632, 95% CI: 0.399–0.999), education (OR = 0.516, 95% CI: 0.434–0.612), gender (OR = 1.865, 95% CI: 1.165–2.987), and age (OR = 3.406, 95% CI: 2.345–4.947). Education was a predictor of lack of appreciation of infection risk (OR = 0.519, 95% CI: 0.449–0.599) and practice (OR = 0.481, 95% CI: 0.396–0.584). Our findings indicate that SFTS-related health education programs are required for females; participants from Qianshan Prefecture; those with an occupation of farmer, retiree, houseworker, or unemployed; elderly participants; and those with low education. Large-scale sustainable health education programs focusing on the target populations are urgently needed in endemic areas.

In March 2016, an outbreak of Rift Valley fever (RVF) was identified in Kabale district, southwestern Uganda. A comprehensive outbreak investigation was initiated, including human, livestock, and mosquito vector investigations. Overall, four cases of acute, nonfatal human disease were identified, three by RVF virus (RVFV) reverse transcriptase polymerase chain reaction (RT-PCR), and one by IgM and IgG serology. Investigations of cattle, sheep, and goat samples from homes and villages of confirmed and probable RVF cases and the Kabale central abattoir found that eight of 83 (10%) animals were positive for RVFV by IgG serology; one goat from the home of a confirmed case tested positive by RT-PCR. Whole genome sequencing from three clinical specimens was performed and phylogenetic analysis inferred the relatedness of 2016 RVFV with the 2006–2007 Kenya-2 clade, suggesting previous introduction of RVFV into southwestern Uganda. An entomological survey identified three of 298 pools (1%) of Aedes and Coquillettidia species that were RVFV positive by RT-PCR. This was the first identification of RVFV in Uganda in 48 years and the 10th independent viral hemorrhagic fever outbreak to be confirmed in Uganda since 2010.

The contribution of respiratory viruses to acute febrile illness (AFI) burden is poorly characterized. We describe the prevalence, seasonality, and clinical features of respiratory viral infection among AFI admissions in Sri Lanka. We enrolled AFI patients ≥ 1 year of age admitted to a tertiary care hospital in southern Sri Lanka, June 2012–October 2014. We collected epidemiologic/clinical data and a nasal or nasopharyngeal sample that was tested using polymerase chain reaction (Luminex NxTAG, Austin, TX). We determined associations between weather data and respiratory viral activity using the Spearman correlation and assessed respiratory virus seasonality using a Program for Appropriate Technology definition. Bivariable and multivariable regression analyses were conducted to identify features associated with respiratory virus detection. Among 964 patients, median age was 26.2 years (interquartile range 14.6–39.9) and 646 (67.0%) were male. One-fifth (203, 21.1%) had respiratory virus detected: 13.9% influenza, 1.4% human enterovirus/rhinovirus, 1.4% parainfluenza virus, 1.1% respiratory syncytial virus, and 1.1% human metapneumovirus. Patients with respiratory virus identified were younger (median 9.8 versus 27.7 years, P < 0.001) and more likely to have respiratory signs and symptoms. Influenza A and respiratory viral activity peaked in February–June each year. Maximum daily temperature was associated with influenza and respiratory viral activity (P = 0.03 each). Patients with respiratory virus were as likely as others to be prescribed antibiotics (55.2% versus 52.6%, P = 0.51), and none reported prior influenza vaccination. Respiratory viral infection was a common cause of AFI. Improved access to vaccines and respiratory diagnostics may help reduce disease burden and inappropriate antibiotic use.

In rural agricultural communities in Africa, particularly those with a single annual harvest, the preharvest period has been associated with increased food insecurity. We estimated the association between seasonal food insecurity and childhood malnutrition in Haydom, Tanzania. Children enrolled in a birth cohort study were followed twice weekly to document food intake and monthly for anthropometry until the age of 2 years. Household food insecurity was reported by caregivers every 6 months. We modeled the seasonality of food insecurity and food consumption, and estimated the impact of birth season on enrollment weight and subsequent malnutrition. Finally, we described the seasonality of admissions for acute malnutrition at a local referral hospital (Haydom Lutheran Hospital) from 2010 to 2015. Food insecurity was highly seasonal, with a peak from December to February. Children born during these 3 months had an average 0.35 z-score (95% CI: 0.12, 0.58) lower enrollment weight than children born in other months. In addition, weight-for-length z-scores measured in these months were on average 0.15 z-scores lower (95% CI: 0.10, 0.20) than that in other months, adjusting for enrollment weight and seasonal infectious diseases, and this disparity was sustained up to the age of 2 years. Correspondingly, the number of admissions with acute malnutrition at the local hospital was highest at this time, with twice as many cases in December–February compared with June–August. We identified acute and chronic malnutrition associated with seasonal food insecurity and intake. Targeting of prenatal care and child-feeding interventions during high food insecurity months may help reduce child malnutrition.

Bacillus pumilus has rarely been reported as a cause of human infections. We report a case of a B. pumilus causing food poisoning in an adult male. A 51-year-old Japanese man complained of severe abdominal cramps, fever with chills, diarrhea, dizziness, and loss of appetite after eating reheated rice with stewed minced meat purchased from a Kenyan restaurant. Bacillus pumilus was isolated from blood culture and was identified using a biochemical test and 16S rRNA gene sequencing analysis. The patient was treated with probiotics and ciprofloxacin and recovered after 3 days. To our knowledge, this is the first report describing the potential role of B. pumilus as a foodborne pathogen in Kenya and highlights the importance of good hygiene and food preparation practices.

Mass drug administration (MDA) with azithromycin may reduce under-5 child mortality (U5M) in sub-Saharan Africa. Here, we conducted a pooled analysis of all published cluster-randomized trials evaluating the effect of azithromycin MDA on child mortality. We pooled data from cluster-randomized trials randomizing communities to azithromycin MDA versus control. We calculated mortality rates in the azithromycin and control arms in each study, and by country for multisite studies including multiple countries. We conducted a two-stage individual community data meta-analysis to estimate the effect of azithromycin for prevention of child mortality. Three randomized controlled trials in four countries (Ethiopia, Malawi, Niger, and Tanzania) were identified. The overall pooled mortality rate was 15.9 per 1,000 person-years (95% confidence interval [CI]: 15.5–16.3). The pooled mortality rate was lower in azithromycin-treated communities than in placebo-treated communities (14.7 deaths per 1,000 person-years, 95% CI: 14.2–15.3 versus 17.2 deaths per 1,000 person-years, 95% CI: 16.5–17.8). There was a 14.4% reduction in all-cause child mortality in communities receiving azithromycin MDA (95% CI: 6.3–21.7% reduction, P = 0.0007). All-cause U5M was lower in communities receiving azithromycin MDA than in control communities, suggesting that azithromycin MDA could be a new tool to reduce child mortality in sub-Saharan Africa. However, heterogeneity in effect estimates suggests that the magnitude of the effect may vary in time and space and is currently not predictable.

A region-wide population-based post–mass drug administration (MDA) coverage survey was conducted 3 weeks following the 2016 trachoma MDA in Amhara, Ethiopia. The prevalence of self-reported side effects was assessed among those who self-reported receiving azithromycin. A total of 16,773 individuals from 5,129 households reported taking azithromycin during the 2016 MDA in Amhara. The regional prevalence of any self-reported side effect was 9.6% (95% CI: 8.3–11.2%) and ranged from 3.9% to 12.4% among the 10 zones. The most common reported side effects were abdominal pain (53.1%), nausea (21.7%), vomiting (12.8%), and diarrhea (12.5%). Side-effect prevalence among female members was higher than in male members (11.6% versus 7.6%; P < 0.001) and increased with age. After an average of 8 years of annual MDA, the prevalence of self-reported side effects was less than 10% in this population.

Praziquantel is widely used for treating parasitic infections globally, especially in countries with endemic schistosomiasis. However, severe hypersensitivity to praziquantel has rarely been reported. We report the case of a 30-year-old Japanese man who developed acute generalized exanthematous pustulosis (AGEP), which is a rare and severe cutaneous reaction usually triggered by drugs, after taking praziquantel. During medical examination, eggs of Diphyllobothrium nihonkaiense were found in his stool. He took praziquantel 600 mg for 1 day and developed skin rashes and fever the next day. Pruritic generalized maculopapular erythematous eruptions were observed over the entire body. He had elevated white blood cell count, liver enzymes, and C-reactive protein level. We prescribed acetaminophen, fexofenadine hydrochloride, loxoprofen sodium, and topical ointments including difluprednate and hydrocortisone. Over the next 3 days, he developed pinhead-sized, non-follicular pustules on his diffusely erythematous skin. Histological findings of the pustular lesion showed spongiform subcorneal pustules with perivascular inflammatory cells. Approximately 8 days after taking praziquantel, the pustules resolved with desquamation. He became afebrile on day 9 and his laboratory parameters returned to normal levels on day 16. He was diagnosed with AGEP caused by praziquantel. Physicians need to be aware that praziquantel could cause AGEP, although it is generally considered a safe drug.

Human protothecosis is a rare algal infection caused by Prototheca; it is a ubiquitous achlorophyllic alga, which rarely causes human disease. Currently, the pathogenesis remains unclear and no treatment options have been elucidated. We present a case of olecranon bursitis caused by Prototheca wickerhamii in an immunocompromised patient. A 45-year-old man presented with left elbow pain after scraping his elbow on a tree. He reported significant pain and swelling of the elbow after injury, which resolved without intervention. He was diagnosed with HIV/AIDS infection and started on antiretroviral therapy. Afterward, he experienced recurrent elbow swelling and pain; an incision and drainage was performed and cultures demonstrated P. wickerhamii. Unsuccessful treatment with oral voriconazole led to an attempt at therapy with parental amphotericin and oral doxycycline; however the patient left against medical advice. He presented to our facility and both parental amphotericin and doxycycline were initiated with planned outpatient bursectomy. He clinically improved on that regimen but left against medical advice before completing his recommended course of IV amphotericin and oral doxycycline. Patients diagnosed with disseminated protothecosis can have a mortality rate upward of 67%. Given the rarity of this pathogen, no official treatment guidelines exist and there are few studies analyzing the antimicrobial susceptibility of Prototheca. Management is challenging because of slow-growing nature of the algae, paucity of research studies, and limited susceptibility of this pathogen. This case adds to the limited body of literature by demonstrating the clinical presentation of protothecosis and highlighting the pathology and current treatment options.

This study discusses a historical patient series and is designed to describe clinical and epidemiological characteristics of human sporotrichosis in the state of Espírito Santo, Brazil. Data were derived from patients treated at the Infectious Diseases service of Cassiano Antônio Moraes University Hospital in Vitória, the state capital, from July 1982 to June 2012. A total of 171 patients were diagnosed with sporotrichosis, mostly men (80.7%) with a median age of 33 years and 5 months. We can presume an approximate average incidence rate of 4.9 cases per 100,000 inhabitants during the studied period. All the patients were involved in occupational or leisure activities with direct contact with soil or plants. Most cases were recorded in the mountainous region of the state during the hot and rainy periods. The average time elapsed from lesion progression to diagnosis was 3 months, with the lymphocutaneous form being the most common (70.2%), followed by the fixed cutaneous form (28.6%). Diagnosis was confirmed in 93.6% of the cases by culturing Sporothrix spp. in Sabouraud dextrose agar, and from the clinical features in the remaining cases. Aspiration of cutaneous nodule secretions was the best method for the collection of clinical specimens for disease diagnosis. A 25% saturated solution of potassium iodide (SSKI) was provided to almost all patients (98.8%), with therapeutic success. In conclusion, in this retrospective study in the state of Espírito Santo, we found that sporotrichosis affects primarily the ≥ 10-year-old population, and the most common presentation is the lymphocutaneous form affecting the lower and upper limbs, and the infection appeared to be acquired predominantly through occupational activities. Treatment with SSKI was safe and effective.

Bothrops asper, a highly venomous pit viper distributed from Colombia and northwestern Peru in South America to southern Mexico, is responsible for most snake bites in Central America, affecting especially young agricultural workers. A 17-year-old male from a rural area in northern Honduras was admitted at San Francisco Hospital after a B. asper bite that had occurred 3 days earlier. The puncture wounds were located on the first toe of the right foot. On the second day of admission, the patient developed dyspnea. A physical examination revealed hypoventilation of the left lung with dullness on 75% of the left lung. Left pleural effusion, approximately 90%, was observed on the chest X-ray. The patient was diagnosed with hemothorax, and a thoracostomy drained 1,350 mL of serosanguineous fluid, followed by the installation of a wet suction control system (Pleur-evac®). After 10 days, the patient was discharged. This case illustrates the diversity of hemorrhagic manifestations in envenomations by B. asper.

Enteric pathogens can be transmitted within the household and the surrounding neighborhood. The objective of this study was to understand the effect of neighborhood-level sanitation coverage on contamination of the household environment with levels of fecal indicator bacteria in rural Bangladesh. We conducted spot-check observations of sanitation facilities in neighboring households (NHs) within a 20-m radius of target households with children aged 6–24 months. Sanitation facilities were defined as improved (a private pit latrine with a slab or better) or unimproved. Fecal coliforms (FCs) on children’s hands and sentinel toy balls were measured and used as indicators of household-level fecal contamination. We visited 1,784 NHs surrounding 428 target households. On average, sentinel toy balls had 2.11(standard deviation [SD] = 1.37) log10 colony-forming units (CFUs) of FCs/toy ball and children’s hands had 2.23 (SD = 1.15) log10 CFU of FCs/two hands. Access to 100% private improved sanitation coverage in the neighborhood was associated with a small and statistically insignificant difference in contamination of sentinel toy balls (difference in means = −0.13 log10 CFU/toy ball; 95% confidence intervals [CI]: −0.64, 0.39; P = 0.63) and children’s hands (difference in means = −0.11 log10 CFU/two hands; 95% CI: −0.53, 0.32; P = 0.62). Improved sanitation coverage in the neighborhood had limited measurable effect on FCs in the target household environment. Other factors such as access to improved sanitation in the household, absence of cow dung, presence of appropriate water drainage, and optimal handwashing practice may be more important in reducing FCs in the household environment.

Unsafe drinking water and poor sanitation and hygiene lead to deterioration of the child health condition in low- and middle-income countries. This study aimed to evaluate the nutritional and health status of children living in an urban slum and to clarify the factors contributing to undernutrition and diarrhea prevalence by focusing on water, sanitation, and hygiene from three viewpoints: household environments, child personal hygiene practices, and knowledge and awareness. The study was conducted at a preschool and two elementary schools in the densely populated area of Bandung, Indonesia. Participants were 228 pairs of children and their caretakers. The survey involved 1) anthropometric measurements (height and weight), 2) handwashing observation using a checklist, and 3) questionnaires. On multivariate logistic regression analysis, not using a towel for handwashing practices (adjusted odds ratio [AOR] = 2.37; 95% confidence interval [CI] = 1.13–4.96) was significantly associated with an increased risk of stunting. Regarding household environments, children from households using tap water as drinking water were significantly associated with an increased risk of stunting and thinness compared with households using tank water (AOR = 2.26; 95% CI = 1.03–4.93; and AOR = 2.88; 95% CI = 1.13–7.35, respectively). Moreover, children from households using open containers for water storage were significantly associated with an increased risk of diarrhea (AOR = 5.01; 95% CI = 1.08–23.15). Therefore, drinking water management at home and proper personal hygiene practices of children are important for maintaining and promoting child health in urban Indonesian slums.

There is increasing appreciation that latrine access does not imply use—many individuals who own latrines do not consistently use them. Little is known, however, about the determinants of latrine use, particularly among those with variable defecation behaviors. Using the integrated behavior model of water, sanitation, and hygiene framework, we sought to characterize determinants of latrine use in rural Ecuador. We interviewed 197 adults living in three communities with a survey consisting of 70 psychosocial defecation-related questions. Questions were excluded from analysis if responses lacked variability or at least 10% of respondents did not provide a definitive answer. All interviewed individuals had access to a privately owned or shared latrine. We then applied adaptive elastic nets (ENET) and supervised principal component analysis (SPCA) to a reduced dataset of 45 questions among 154 individuals with complete data to select determinants that predict self-reported latrine use. Latrine use was common, but not universal, in the sample (76%). The SPCA model identified six determinants and adaptive ENET selected five determinants. Three indicators were represented in both models—latrine users were more likely to report that their latrine is clean enough to use and also more likely to report daily latrine use; while those reporting that elderly men were not latrine users were less likely to use latrines themselves. Our findings suggest that social norms are important predictors of latrine use, whereas knowledge of the health benefits of sanitation may not be as important. These determinants are informative for promotion of latrine adoption.

We assessed the impact of handwashing promotion on reported respiratory illness as a secondary outcome from among > 60,000 low-income households enrolled in a cluster-randomized trial conducted in Bangladesh. Ninety geographic clusters were randomly allocated into three groups: cholera-vaccine-only; vaccine-plus-behavior-change (handwashing promotion and drinking water chlorination); and control. Data on respiratory illness (fever plus either cough or nasal congestion or breathing difficulty within previous 2 days) and intervention uptake (presence of soap and water at handwashing station) were collected through monthly surveys conducted among a different subset of randomly selected households during the intervention period. We determined respiratory illness prevalence across groups and used log-binomial regression to examine the association between respiratory illness and presence of soap and water in the handwashing station. Results were adjusted for age, gender, wealth, and cluster-randomized design. The vaccine-plus-behavior-change group had more handwashing stations with soap and water present than controls (45% versus 25%; P < 0.001). Reported respiratory illness prevalence was similar across groups (vaccine-plus-behavior-change versus control: 2.8% versus 2.9%; 95% confidence interval [CI]: −0.008, 0.006; P = 0.6; cholera-vaccine-only versus control: 3.0% versus 2.9%; 95% CI: −0.006, 0.009; P = 0.4). Irrespective of intervention assignment, respiratory illness was lower among people who had soap and water present in the handwashing station than among those who did not (risk ratioadjusted: 0.82; 95% CI: 0.69–0.98). With modest uptake of the handwashing intervention, we found no impact of this large-scale intervention on respiratory illness. However, those who actually had a handwashing station with soap and water had less illness. This suggests improving the effectiveness of handwashing promotion in achieving sustained behavior change could result in health benefits.