The American Journal of Tropical Medicine and Hygiene - Volume 100, Issue 4, 2019

Gains in reducing childhood disease burden rely heavily on effective means of preventing environmental exposures. For many environmental health interventions, such as point-of-use water treatment, sanitation, or cookstoves, exposures are strongly influenced by user behaviors and the degree to which participants adhere to the prescribed preventive measures. In this commentary, we articulate the need for increased attention on user behaviors—critically, the careful measurement and inclusion of compliance—to strengthen exposure assessment and health impact trials in environmental health intervention research. We focus here on water, sanitation, and hygiene interventions to illustrate the problem with the understanding that this issue extends to other environmental health interventions.

A panel of experts from the Infectious Disease Society of America and The American Society of Tropical Medicine and Hygiene recently published guidelines for management of neurocysticercosis, showing that clinical manifestations as well as the stage of involution and the anatomical location of parasites must be taken into account before the start of a rational therapy. Soon thereafter, isolated opinions attempted to discredit these guidelines, arguing insufficient or inadequate evidence and suggesting that they should not be followed worldwide. In view of these conflicting reports, it is appropriate to review the origin and evolution of the controversy on the medical treatment of neurocysticercosis.

Dengue virus (DENV) causes asymptomatic to severe life-threatening infections and affects millions of people worldwide. Autophagy, a cellular degradative pathway, has both proviral and antiviral functions. Dengue virus triggers the autophagy pathway for the successful replication of its genome. However, the exact mechanism and the viral factors involved in activating this pathway remain unclear. This review summarizes the existing knowledge on the mechanism of autophagy induction and its significance during DENV infection.

Isolated renal mucormycosis in immunocompetent hosts is a rare entity. We present the largest case series of isolated renal mucormycosis in immunocompetent hosts. Retrospective data of isolated renal mucormycosis from March 2012 to June 2017 was reviewed. Fifteen patients of isolated renal mucormycosis were identified. Contrast-enhanced computed tomography scan showed enlarged globular kidneys with decreased or patchy enhancement, perinephric stranding and thickened Gerota’s fascia in all patients. Ten patients with unilateral involvement underwent nephrectomy and two of four patients with bilateral renal mucormycosis underwent bilateral nephrectomy. Two patients were managed with intravenous antifungal therapy alone. Overall, the mortality rate in our series was 40% (6/15). Isolated renal mucormycosis in healthy immunocompetent hosts is an emerging new entity. Prompt diagnosis based on the characteristic clinical and radiological picture and starting high-dose antifungal therapy at least 24 hours before surgical debridement offer the best chance of survival in these patients.

American cutaneous leishmaniasis (ACL) is a common and important vector-borne parasitic zoonosis in Panamá. Here, we study Leishmania spp. infection rates and blood-feeding patterns among common sand flies in Trinidad de Las Minas, a rural community with hyperendemic ACL transmission, and where a deltamethrin fogging trial was performed. Sand flies were collected from April 2010 to June 2011 with light traps installed inside and in the peridomicile of 24 houses. We restricted our analysis to the most abundant species at the study site: Lutzomyia trapidoi, Lutzomyia gomezi, Lutzomyia panamensis, Lutzomyia triramula, and Lutzomyia dysponeta. We detected Leishmania spp. infection in sand flies by polymerase chain reaction (PCR) amplification of the internal transcribed spacer region 1 (ITS-1) in pooled females (1–10 females per pool). Host species of engorged sand flies were identified using a cytochrome b PCR. From 455 sand fly pools analyzed, 255 pools were positive for Leishmania spp., with an estimated infection rate (confidence interval) of 0.096 [0.080–0.115] before the deltamethrin fogging which slightly, but not significantly (P > 0.05), increased to 0.116 [0.098–0.136] after the deltamethrin fogging. Blood meal analysis suggested that pigs, goats, and birds were the most common sand fly blood sources, followed by humans and domestic dogs. DNA sequencing from a subsample of ITS-1 positive pools suggests that Leishmania panamensis, Leishmania naiffi, and other Leishmania spp. were the parasite species infecting the most common vectors at the study site. Our data confirm an association between sand fly species, humans, domestic dogs, and pigs and Leishmania spp. parasites in rural Panamá.

We analyzed the association between insulin-like growth factor-I (IGF-I) and the pathogenesis of anemia during active visceral leishmaniasis (VL). Serum levels of IGF-I, IGF-binding protein 3 (IGFBP3), and cytokines were measured in samples from individuals with active VL and cured VL, asymptomatic Leishmania-infected, and noninfected individuals. Then, we extended our analysis to VL dogs to evaluate hematimetric parameters, bone marrow alterations, and cytokine and IGF-I expression. We identified a positive correlation between lower IGF-I and IGFBP3 levels in active VL patients and lower hemoglobin levels. In infected dogs, there was a positive correlation between lower IGF-I expression in the bone marrow and lower peripheral blood hematocrit and hemoglobin levels. There was no correlation between decreased IGF-I level/expression and any measured cytokine serum levels in either host. The data suggest that low IGF-I expression is associated with pathogenesis of anemia in active VL, primarily in severe cases, by mechanisms other than alterations in cytokine production.

B-cells have a spectrum of functions ranging from antibody production to antigen presentation and have additional vital roles in immune mechanisms. There is rudimentary knowledge about the role of B-cells in intracellular infections with contradictory findings. We explored the role of B-cell dysfunctions in visceral leishmaniasis (VL) pathogenesis in terms of the phenotypic and functional properties of B-cells during the course of disease. This study was performed on blood and splenic aspirates (SA) of VL cases pre- and post-treatment. Whole blood was used for flow cytometric studies for determining the profiles of B-cells at different time-points of treatment. Peripheral blood mononuclear cells were used for magnetic purification of B-cells, for transcriptional studies by real-time polymerase chain reaction (RT-PCR). Serum/plasma was used for direct agglutination test for determining parasite-specific antibodies and SA were used for scoring the presence of parasite by microscopic examination. Flow cytometric studies depicted decreased B-cell percentages during the entire course of disease and attainment of exhaustive phenotype with tissue-like memory cell markers, indicative of B-cell dysfunctions in VL. In addition, B-cells had compromised abilities of antigen processing and presentation and altered levels of B-lymphocyte–induced maturation protein-1 (Blimp-1). Blimp-1 expression goes hand in hand with B-cell maturation antigen and transmembrane activator and calcium modulator (TACI) and cyclophilin ligand interactor, suggestive of its role in promoting plasma cell survival and antibody production. Elevated level of VL-specific antibody titre was directly correlated with exhausted phenotype and also with disease severity during VL. This study indicated for impaired B-cell functions during chronic infection which may lead to pathological consequences in human VL.

The standard in vitro cultivation procedure for Plasmodium falciparum requires gas exchange and a microaerophilic atmosphere. A novel system using a commercially available cell culture device (Petaka G3™; Celartia Ltd., Powell, OH) was assessed for long-term cultivation of a P. falciparum reference laboratory clone in normal air. Parasite growth during 30 days was similar, or better, in Petaka G3 than that in the standard cultivation method with gas exchange in a CO2 incubator. The successful cultivation of P. falciparum in the Petaka G3 device suggests that low O2 content available in hemoglobin and dissolved gas in the blood is sufficient for long-term cultivation. This finding may open the way to novel methods to cultivate and adapt P. falciparum field isolates to in vitro conditions with more ease.

In this study, we reviewed imported malaria cases observed at the National Center for Global Health and Medicine, Tokyo, between 2005 and 2016, to comprehend their demographic and clinical characteristics. Data on 169 cases were used to analyze demographic information; data on 146 cases were used for the analysis of clinical information. The median patients’ age was 34 years, and 79.3% of them were male. The proportion of non-Japanese patients increased and surpassed that of Japanese patients after 2015. In 82.2% of the cases, the region of acquisition was Africa, and Plasmodium falciparum was the dominant species (74.0%) followed by Plasmodium vivax (15.4%). We observed 19 (18.4%, 19/103) severe falciparum malaria cases. Mefloquine was the most commonly used drug for treatment until the early 2010s; atovaquone/proguanil was the most commonly used after its licensure in 2013. Although none of the patients died, four recrudescence episodes after artemether/lumefantrine (A/L) treatment and one relapse episode were observed. Overall, malaria was diagnosed on median day 4 of illness, and, thereon, treatment was initiated without delay. Diagnosis on day 5 or later was significantly associated with severe disease in Japanese cases (odds ratio = 4.1; 95% CI = 1.2–14.3). We observed a dominance of falciparum malaria, an increase in the number of non-Japanese cases, late treatment failure after A/L treatment, a low relapse rate, and an association between delayed malaria diagnosis and higher disease severity. Pretravel care and early diagnosis are necessary to reduce malaria-related mortality and morbidity in settings such as ours.

We aimed to identify clinical and laboratory predictors of mortality in children from a malaria-endemic area of Papua New Guinea hospitalized for severe illness. Children aged 0.5–10 years presenting with any WHO-defined feature of severe malarial illness were eligible for recruitment. Each child was assessed with a detailed clinical examination, blood film microscopy, malaria rapid diagnostic testing (RDT), a full blood examination, and blood glucose and lactate concentrations. Clinical care was coordinated by local medical staff in accordance with national guidelines. Daily study assessments were conducted until death or discharge. Other biochemical tests and malaria polymerase chain reaction (PCR) tests were performed subsequently. Logistic regression identified independent predictors of death. Of 787 evaluable children with severe illness, 336 had confirmed severe malaria (microscopy and PCR positive) and 58 (6.6%) died during hospitalization. The independent predictors of mortality were hyperlactatemia (adjusted odds ratio [95% CI]: 2.85 [1.24–6.41], P = 0.01), malnutrition (2.92 [1.36–6.23], P = 0.005), renal impairment (3.85 [1.53–9.24], P = 0.002), plasma albumin (0.93 [0.88–0.98] for a 1 g/L increase, P = 0.004), and Blantyre coma score (BCS) ≤ 2 (10.3 [4.77–23.0] versus a normal BCS, P < 0.0001). Confirmed severe malaria (0.11 [0.03–0.30] versus non-malarial severe illness, P < 0.0001) was independently associated with lower mortality. Although established risk factors were evident, malaria was inversely associated with mortality. This highlights the importance of accurate diagnosis through blood film microscopy, RDTs, and, if available, PCR to both guide management and provide valid epidemiological data.

We attempted to identify Plasmodium falciparum histidine–rich protein 2/3 (pfhrp2/3) deletions among rapid diagnostic test (RDT)–negative but PCR- or microscopy-positive P. falciparum–infected individuals in areas of low transmission (Choma District, 2009–2011) and high transmission (Nchelenge District, 2015–2017) in Zambia. Through community-based surveys, 5,167 participants were screened at 1,147 households by P. falciparum histidine-rich protein 2 (PfHRP2)-based RDTs. Slides were made and dried blood spots were obtained for molecular analysis. Of 28 samples with detectable P. falciparum DNA, none from Nchelenge District were pfhrp2/3 negative. All eight samples from Choma District had detectable pfhrp3 genes, but pfhrp2 was undetectable in three. DNA concentrations of pfhrp2-negative samples were low (< 0.001 ng/μL). These findings suggest that PfHRP2-based RDTs remain effective tools for malaria diagnosis in Nchelenge District, but further study is warranted to understand the potential for pfhrp2/3 deletions in southern Zambia where malaria transmission declined over the past decade.

During the building of the Thai–Burma railway in 1943 Australian and British prisoners of war died at high rates from tropical infections and nutritional deficiencies. Mortality records from “F” Force (n = 7,000) showed nearly half (44%) of the soldiers perished in a single year, yet only 4% of these deaths were primarily attributed to malaria, with another 7% where malaria was listed as a major contributing cause. Case fatality rates were < 1%, with nearly all soldiers chronically infected with Plasmodium vivax > Plasmodium falciparum. Separate labor camp point prevalence malaria rates by microscopy ranged from 28% to 69% (median 54%) despite intermittent quinine suppression. During complex public health emergencies, malaria mortality may be disguised by its combination with other common infections and nutritional deficiencies.

The U.S. President’s Malaria Initiative–funded MalariaCare project implemented an external quality assurance scheme to support malaria diagnostics and case management across a spectrum of health facilities in participating African countries. A component of this program was a 5-day, malaria diagnostic competency assessment (MDCA) course for health facility laboratory staff conducting malaria microscopy. The MDCA course provided a method to quantify participant skill levels in microscopic examination of malaria across three major diagnosis areas: parasite detection, species identification, and parasite quantification. A total of 817 central-, regional-, and peripheral-level microscopists from 45 MDCA courses across nine African countries were included in the analysis. Differences in mean scores with respect to daily marginal performance were positive and statistically significant (P < 0.001) for each challenge type across all participants combined. From pretest to assessment day 4, mean scores for parasite detection, species identification, and parasite quantification increased by 19.1, 34.9, and 38.2 percentage points, respectively. In addition, sensitivity and specificity increased by 20.8 and 13.8 percentage points, respectively, by assessment day 4. Furthermore, the ability of MDCA participants to accurately report Plasmodium falciparum species when present increased from 44.5% at pretest to 67.1% by assessment day 4. The MDCA course rapidly improved the microscopy performance of participants over a short period of time. Because of its rigor, the MDCA course could serve as a mechanism for measuring laboratory staff performance against country-specific minimum competency standards and could easily be adapted to serve as a national certification course.

Between 2012 and 2017, the U.S. President’s Malaria Initiative–funded MalariaCare project supported national malaria control programs in sub-Saharan Africa to implement a case management quality assurance (QA) system for malaria and other febrile illnesses. A major component of the system was outreach training and supportive supervision (OTSS), whereby trained government health personnel visited health facilities to observe health-care practices using a standard checklist, to provide individualized feedback to staff, and to develop health facility–wide action plans based on observation and review of facility registers. Based on MalariaCare’s experience, facilitating visits to more than 5,600 health facilities in nine countries, we found that programs seeking to implement similar supportive supervision schemes should consider ensuring the following: 1) develop a practical checklist that balances information gathering and mentorship; 2) establish basic competency criteria for supervisors and periodically assess supervisor performance in the field; 3) conduct both technical skills training and supervision skills training; 4) establish criteria for selecting facilities to conduct OTSS and determine the appropriate frequency of visits; and 5) use electronic data collection systems where possible. Cost will also be a significant consideration: the average cost per OTSS visit ranged from $44 to $333. Significant variation in costs was due to factors such as travel time, allowances for government personnel, length of the visit, and involvement of central level officials. Because the cost of conducting supportive supervision prohibits regularly visiting all health facilities, internal QA measures could also be considered as alternative or complementary activities to supportive supervision.

Although light microscopy is the reference standard for diagnosing malaria, maintaining skills over time can be challenging. Between 2015 and 2017, the U.S. President’s Malaria Initiative–funded MalariaCare project supported outreach training and supportive supervision (OTSS) visits at 1,037 health facilities in seven African countries to improve performance in microscopy slide preparation, staining, and reading. During these visits, supervisors observed and provided feedback to health-care workers (HCWs) performing malaria microscopy using a 30-step checklist. Of the steps observed in facilities with at least three visits, the proportion of HCWs that performed each step correctly at baseline ranged from 63.2% to 94.2%. The change in the proportion of HCWs performing steps correctly by the third visit ranged from 16.7 to 23.6 percentage points (n = 916 observations). To assess the overall improvement, facility scores were calculated based on the steps performed correctly during each visit. The mean score at baseline was 85.7%, demonstrating a high level of performance before OTSS. Regression analysis predicted an improvement in facility scores of 3.6 percentage points (P < 0.001) after three visits across all countries. In reference-level facilities with consistently high performance on microscopy procedures and parasite detection, quality assurance (QA) mechanisms could prioritize more advanced skills, such as proficiency testing for parasite counting and species identification. However, in settings with high staff turnover and declining use of microscopy in favor of rapid diagnostic tests, additional supervision visits and/or additional QA measures may be required to improve and maintain performance.

Rapid diagnostic tests (RDTs) are one of the primary tools used for parasitological confirmation of suspected cases of malaria. To ensure accurate results, health-care workers (HCWs) must conduct the RDT test correctly. Trained supervisors visited 3,603 facilities to assess RDT testing performance and conduct outreach training and supportive supervision activities in eight African countries between 2015 and 2017, using a 12-point checklist to determine if key steps were being performed. The proportion of HCWs performing each step correctly improved between 1.1 and 21.0 percentage points between the first and third visits. Health-care worker scores were averaged to calculate facility scores, which were found to be high: the average score across all facilities was 85% during the first visit and increased to 91% during the third visit. A regression analysis of these facility scores estimated that, holding key facility factors equal, facility performance improved by 5.3 percentage points from the first to the second visit (P < 0.001), but performance improved only by 0.6 percentage points (P = 0.10) between the second and third visits. Factors strongly associated with higher scores included the presence of a laboratory worker at the facility and the presence of at least one staff member with previous formal training in malaria RDTs. Findings confirm that a comprehensive quality assurance system of training and supportive supervision consistently, and often significantly, improves RDT performance.

Since 2010, the WHO has recommended that clinical decision-making for malaria case management be performed based on the results of a parasitological test result. Between 2015 and 2017, the U.S. President’s Malaria Initiative–funded MalariaCare project supported the implementation of this practice in eight sub-Saharan African countries through 5,382 outreach training and supportive supervision visits to 3,563 health facilities. During these visits, trained government supervisors used a 25-point checklist to observe clinicians’ performance in outpatient departments, and then provided structured mentoring and action planning. At baseline, more than 90% of facilities demonstrated a good understanding of WHO recommendations—when tests should be ordered, using test results to develop an accurate final diagnosis, severity assessment, and providing the correct prescription. However, significant deficits were found in history taking, conducting a physical examination, and communicating with patients and their caregivers. After three visits, worker performance demonstrated steady improvement—in particular, with checking for factors associated with increased morbidity and mortality: one sign of severe malaria (72.9–85.5%), pregnancy (81.1–87.4%), and anemia (77.2–86.4%). A regression analysis predicted an overall improvement in clinical performance of 6.3% (P < 0.001) by the third visit. These findings indicate that in most health facilities, there is good baseline knowledge on the processes of quality clinical management, but further training and on-site mentoring are needed to improve the clinical interaction that focuses on second-order decision-making, such as severity of illness, management of non-malarial fever, and completing the patient–provider communication loop.

Although on-site supervision programs are implemented in many countries to assess and improve the quality of care, few publications have described the use of electronic tools during health facility supervision. The President’s Malaria Initiative–funded MalariaCare project developed the MalariaCare Electronic Data System (EDS), a custom-built, open-source, Java-based, Android application that links to District Health Information Software 2, for data storage and visualization. The EDS was used during supervision visits at 4,951 health facilities across seven countries in Africa. The introduction of the EDS led to dramatic improvements in both completeness and timeliness of data on the quality of care provided for febrile patients. The EDS improved data completeness by 47 percentage points (42–89%) on average when compared with paper-based data collection. The average time from data submission to a final data analysis product dropped from over 5 months to 1 month. With more complete and timely data available, the Ministry of Health and the National Malaria Control Program (NMCP) staff could more effectively plan corrective actions and promptly allocate resources, ultimately leading to several improvements in the quality of malaria case management. Although government staff used supervision data during MalariaCare-supported lessons learned workshops to develop plans that led to improvements in quality of care, data use outside of these workshops has been limited. Additional efforts are required to institutionalize the use of supervision data within ministries of health and NMCPs.

Human African trypanosomiasis is close to elimination in several countries in sub-Saharan Africa. The diagnosis and treatment is currently rapidly being integrated into first-line health services. We aimed to document the perspective of stakeholders on this integration process. We conducted 12 focus groups with communities in three health zones of the Democratic Republic of the Congo and held 32 interviews with health-care providers, managers, policy makers, and public health experts. The topic guide focused on enabling and blocking factors related to the integrated diagnosis and treatment approach. The data were analyzed with NVivo (QSR International, Melbourne, Australia) using a thematic analysis process. The results showed that the community mostly welcomed integrated care for diagnosis and treatment of sleeping sickness, as they value the proximity of first-line health services, but feared possible financial barriers. Health-care professionals thought integration contributed to the elimination goal but identified several implementation challenges, such as the lack of skills, equipment, motivation and financial resources in these basic health services. Patients often use multiple therapeutic itineraries that do not necessarily lead them to health centers where screening is available. Financial barriers are important, as health care is not free in first-line health centers, in contrast to the population screening campaigns. Communities and providers signal several challenges regarding the integration process. To succeed, the required training of health professionals, as well as staff deployment and remuneration policy and the financial barriers in the primary care system need to be addressed, to ensure coverage for those most in need.

Triatoma sordida is among the main Brazilian species considered as Chagas disease vectors. The genetic studies are directed mainly to phylogenetic questions because this species possibly have suffered cryptic speciation. Furthermore, there are few studies that analyzed the structure and genetic variability of specimens from Brazil and that showed low genetic diversity and strong genetic structuring of the population samples. Therefore, because of great epidemiological importance of T. sordida and mainly the restriction of genetic characterization of this vector only for populations of Minas Gerais state, this article performs a genetic analysis of the T. sordida from seven different Brazilian states (representing different biomes), by means of cytogenetic markers. All analyzed specimens presents the same cytogenetic characteristics: early meiotic prophase with several heterochromatic bodies dispersed in the nucleus (CG-rich), being one of them formed by the associated sex chromosomes surrounded by some autosomal heterochromatic regions, meiotic metaphase with most autosomal pairs exhibiting a C-heterochromatic block in one chromosomal end (CG-rich), Y sex chromosome fully heterochromatin (AT-rich), and X chromosome may present a small C-block (CG-rich). These results are important because the chromosomal markers enable to confirm and expand the low genetic diversity for all Brazilian states occupied by T. sordida, suggesting that all Brazilian populations were originated from a small ancestral population and possibly dispersed to other biomes by founder effect. In addition, we suggest that T. sordida from Brazil are not suffering cryptic speciation and we confirm the classification of all Brazilian examples as T. sordida sensu stricto.

Triatomines are vectors of Trypanosoma cruzi, the etiologic agent of Chagas disease. Although the evolutionary process in triatomine is considered as disruptive, cryptic speciation and homoploid hybridization also are possible modes of speciation. Several analyses suggested Triatoma brasiliensis macromelasoma as a product of hybridization between T. brasiliensis and Triatoma juazeirensis. Thus, we analyzed genetic characteristics (chromosomal analysis, genetic distance for the mitochondrial ND1 gene, and the pattern of bands of internal transcribed spacer [ITS]-1) of these species, with emphasis on the phenomenon of homoploid hybridization. All species showed the same cytogenetic characteristics, low genetic distance for ND1 gene, and the same pattern of ITS-1 bands. We consider that these genetic characteristics, together with the large chromatic polymorphism and the viability of experimental crosses possibly are due to the processes of introgression that these species suffered during the process of homoploid hybridization.

Infections due to Loa loa and Mansonella perstans are common yet elusive neglected filariases. Parasitological cure after treatment is very difficult to assess, as adult parasites are not accessible. Therefore, outside transmission areas, patients require a long follow-up period to ascertain the therapeutic outcome, which is impractical for non-sedentary populations such as migrants. We studied the change over time of microfilaremia, eosinophil counts, and antifilarial antibodies tested with a commercial ELISA test (Bordier Affinity Products, Crissier, Switzerland), in a retrospective cohort of patients with confirmed L. loa and M. perstans infections, to evaluate the role of serology in clinical practice. After treatment, all 22 eligible patients diagnosed in our center between 2015 and 2017 reached amicrofilaremia, with microfilarial counts decreasing sharply within 2 months. Paralleling eosinophil counts, antibodies decreased in all patients, 36% of whom reached sero-reversion or near–sero-reversion in < 20 months. These findings suggest that positive serology is not just residual from a past infection, and may be used for diagnosis even when microfilaremia is negative or cannot be performed. Interestingly, antibodies and eosinophil counts increased following some, but not all, re-treatment courses. If the rise in these parameters reflects death of macrofilariae, caution is required in interpreting high eosinophil counts and antibody titers shortly after treatment, as these may reflect no need for further treatment. To optimize patients’ management, it is now pivotal to ascertain the interval between treatment and macrofilarial death and therefore whether re-treatments are required for complete clearance of parasites.

Neurotropism and infiltration by Mycobacterium leprae of peripheral nerves causing neuropathy are well established, but reports of central nervous system (CNS) damage are exceptional. We report CNS magnetic resonance imaging (MRI) abnormalities of the brain and spinal cord as well as lesions in nerve roots and plexus in leprosy patients. Eight patients aged between 17 and 41 years underwent detailed clinical, histopathological, and MRI evaluation. All had prominent sensory–motor deficits with hypopigmented and hypo/anesthetic skin patches and thickened peripheral nerves. All demonstrated M. Leprae DNA in affected peripheral nerve tissue. All received multidrug therapy (MDT). Two patients had brainstem lesions with enhancing facial nuclei and nerves, and one patient had a lesion in the nucleus ambiguus. Two patients had enhancing spinal cord lesions. Follow-up MRI performed in four cases showed resolution of brainstem and cord lesions after starting on MDT. Thickened brachial and lumbosacral plexus nerves were observed in six and two patients, respectively, which partially resolved on follow-up MRI in the two cases who had reimaging. The site and side of the MRI lesions corresponded with the location and side of neurological deficits. This precise clinico-radiological correlation of proximal lesions could be explained by an immune reaction in the gray matter corresponding to the involved peripheral nerves, retrograde axonal and gray matter changes, or infection of the CNS and plexus by lepra bacilli. Further study of the CNS in patients with leprous neuropathy is needed to establish the exact nature of these CNS MRI findings.

Antioquia Department is the state with the highest burden of tuberculosis (TB) in Colombia. Our aim was to determine the risk factors associated with unsuccessful TB treatment in HIV-seropositive and homeless persons, compared with non–HIV-infected and non-homeless persons with TB. We conducted a retrospective cohort study using observational, routinely collected health data from all drug-susceptible TB cases in homeless and/or HIV-seropositive individuals in Antioquia from 2014 to 2016. Unsuccessful TB treatment was defined as individuals having been lost to follow-up, having died, or treatment failure occurrence during the study period. Successful treatment was defined as cure of TB or treatment completion according to the WHO definitions. We identified 544 homeless persons with TB (432 HIV− and 112 HIV+), 835 HIV+ persons with TB and non-homeless, and 5,086 HIV−/non-homeless people with TB. Unsuccessful treatment rates were 19.3% in HIV−/non-homeless persons, 37.4% in non-homeless HIV+ patients, 61.5% in homeless HIV− patients, and 70.3% in homeless HIV+ patients; all rates fall below End TB strategy targets. More than 50% of homeless patients were lost to follow-up. Risk factors associated with unsuccessful treatment were HIV seropositivity, homelessness, male gender, age ≥ 25 years, noncontributory-type health insurance, TB diagnosis made during hospitalization, and previous treatment for TB. These results highlight the challenge of treating TB in the homeless population. These findings should put an onus on TB programs, governments, clinicians, and others involved in the collaborative care of TB patients to pursue innovative strategies to improve treatment success in this population.

Yaws is a neglected tropical disease targeted for eradication by 2020. Kiribati, a Pacific Island nation, was previously endemic for yaws but lacks recent data from which its current endemicity status could be determined. This study tested antibody responses to Treponema pallidum to determine if transmission of yaws is taking place among children in Kiribati. Using a commercially available T. pallidum particle agglutination kit (Serodia®, Fujirebio Inc., Tokyo, Japan), we tested dried blood spots, collected during population-based trachoma prevalence surveys on Tarawa Atoll and Kiritimati Island, for long-lived treponemal antibodies. Dried blood spots from 1,420 children aged 1–9 years were tested. Only two were positive, suggesting T. pallidum is not being widely transmitted among children in the settings sampled. These data require support from additional surveys to demonstrate the absence of clinical signs of disease and molecular evidence of infection, to confirm that yaws is no longer endemic in Kiribati.

Bloodstream infection surveillance conducted from 2008 to 2014 in all 20 hospitals in Sa Kaeo and Nakhon Phanom provinces, Thailand, allowed us to look at disease burden, antibiotic susceptibilities, and recurrent infections caused by extended-spectrum β-lactamase (ESBL)–producing Escherichia coli and Klebsiella pneumoniae. Of 97,832 blood specimens, 3,338 were positive for E. coli and 1,086 for K. pneumoniae. The proportion of E. coli isolates producing ESBL significantly increased from 19% to 22% in 2008–2010 to approximately 30% from 2011 to 2014 (P-value for trend = 0.02), whereas ESBL production among K. pneumoniae cases was 27.4% with no significant trend over time. Incidence of community-onset ESBL-producing E. coli increased from 5.4 per 100,000 population in 2008 to 12.8 in 2014, with the highest rates among persons aged ≥ 70 years at 79 cases per 100,000 persons in 2014. From 2008 to 2014, community-onset ESBL-producing K. pneumoniae incidence was 2.7 per 100,000, with a rate of 12.9 among those aged ≥ 70 years. Although most (93.6% of E. coli and 87.6% of K. pneumoniae) infections were community-onset, hospital-onset infections were twice as likely to be ESBL. Population-based surveillance, as described, is vital to accurately monitor emergence and trends in antimicrobial resistance, and in guiding the development of rational antimicrobial therapy recommendations.

The incidence of murine typhus in Israel has decreased substantially since 1950 to a low of 0.04/100,000 population in 2010. We present the experience of a single university medical center in central Israel. Hospitalized patients serologically positive for Rickettsia typhi by indirect immunofluorescence antibody assay during 2006–2016 were retrospectively identified. Clinical and laboratory data from patients’ charts were used to analyze disease trends and distribution. Seventy-eight patients were studied (mean age: 27.9 years), mostly of Arab ethnicity (68, 87.2%). Seventy-one (91%) patients resided in two large mixed Jewish-Arab cities—Lod and Ramla. The incidence of murine typhus among the Arab population in Lod increased 8.4-fold from 6.4/100,000 in 2006 to a peak of 53.4/100,000 in 2013. The average annual incidence among Arabs in Ramla was 10.1/100,000. Among Jews, incidences were 0.8/100,000 in Lod and 0.4/100,000 in Ramla. The classical triad of fever, headache, and rash was noted in 20.8% patients. Substantial morbidity included prolonged fever before hospitalization and hospital stay (mean of 8.4 and 5.1 days, respectively), and severe complications in six patients, including pneumonitis in three patients, and splenic infarctions, pericardial effusion, and retinitis, each in one. One previously healthy patient died of multiorgan failure. The study describes a high incidence of murine typhus with a recent upsurge in an urban setting in central Israel. High morbidity and a single fatal outcome challenge the concept of murine typhus being a mild disease. The study calls for better rodent control and sanitation measures in the affected neighborhoods.

Among all other viruses, human cytomegalovirus (HCMV) is the most frequent cause of congenital infection worldwide. Strain variation in HCMV may predict severity or outcome of congenital HCMV disease. Previous studies have associated a particular genotype with specific sequelae or more severe illness, but the results were contradictory. There are no previous studies addressing the genotype of HCMV in Iraq. Therefore, the present study is aimed at molecular detection and genotyping of HCMV isolated from symptomatic congenitally/perinatally infected neonates. This prospective study comprised 24 serum samples from symptomatic neonates with congenital/perinatal infection. Viral DNA was extracted from these serum samples; nested polymerase chain reaction was used to amplify the HCMV gB (UL55) gene. Polymerase chain reaction products of the second round of amplification were subjected to direct Sanger sequencing. Bioedit and MEGA5 software (EMBL-EBI, Hinxton, Cambridgeshire, UK) were used for alignment and construction of a phylogenetic tree. Human cytomegalovirus DNA was detected in 23 of 24 samples (95.8%). According to the phylogenetic analysis, three genotypes of the virus were identified; gB1, gB2, and gB3 genotypes. However, the gB4 genotype was not detected. Human cytomegalovirus gB3 was the most frequent genotype: 14 of 24 (58.33%) among symptomatic infected infants, followed by gB1 (6/24; 25%) and gB2 (4/24; 16.67%). A mixed HCMV infection with gB3/gB1 was detected in only one case. Human cytomegalovirus gB3 was the most predominant genotype among symptomatic congenitally/perinatally HCMV-infected neonates. No association was found between B3 genotype and specific clinical presentation. Jaundice was the most common clinical feature among symptomatically infected neonates, followed by hepatosplenomegaly.

The dengue situation in the urban setting of Hanoi city, Vietnam, is emerging, focusing on inner districts. Previous studies showed that a dengue vector control program in Hanoi was not effective because of the lack of adequate engagement of the local government authorities, health sector, and community. This implementation research aimed to explore barriers to implementing community engagement in a dengue vector control program in an urban district of Hanoi city. Ten in-depth interviews and 14 focus group discussions were conducted at Lang Thuong, Khuong Thuong, Tho Quan, and Kim Lien wards in Dong Da district, Hanoi city. Data collection was implemented from April to June 2017. All discussions were recorded and transcribed verbatim. Data were analyzed using the content analysis approach. Secondary data from the dengue vector control program reports were used to support the qualitative evidence. We found that the barriers to implementing effective community engagement were as follows: 1) lack of interest and an attitude of dependency on action from the health sector of local people’s committee, 2) lack of enthusiasm of mass organizations and community leaders, 3) overburdened workloads and lack of communication skills from health sector, 4) low awareness and readiness from community, 5) lack of detailed policy guidelines and low enforcement of related policy, and 6) limited budget. Recommended actions should be made to improve the community engagement in the current resource-limited context of Vietnam by both top-down and bottom-up approaches.

ZIKA virus (ZIKAV) outbreak in Latin America was associated with international concerns of ZIKAV circulation. The lack of vaccine and Food and Drug Administration (FDA)-approved drugs against this virus rendered prevention as the single most effective method to control its spread. Hence, this study aimed to assess Jordanian population knowledge, attitude, and practices toward ZIKAV and its prevention. An anonymous questionnaire was administered to adults in Amman, Jordan. The overall knowledge of participants was poor (mean knowledge score of 13.7/32). Between 75% and 86% of the respondents did not know the highest risk group of ZIKAV infection, its complications, and the major routes of transmission. About 40% of the population did not know that ZIKAV is sexually transmitted. Only 40% of the population believed that prevention measures are effective. Female gender, working in the medical field, having children, and the source of medical information were associated with significantly higher level of knowledge (R 2 = 0.143, P-value < 0.0001). Being pregnant, however, was not associated with a significantly high knowledge score. Physician recommendations and government’s role were the most important predictors of practices toward ZIKAV prevention. Of the 14 returnees from outbreak areas, only six were tested for ZIKAV on coming back and only three continued the use of prevention measures for a sufficient time. Therefore, formulation of a national health policy, preparedness plans against any potential transmission, and organization of educational campaigns to meet the population’s health educational needs are required. Special emphasis should be placed on pregnant women and travelers to/returnees from ZIKAV-affected areas.

The PackH2O water backpack carrier was developed to provide safe storage and relieve stress of head-loading during water transport with traditional containers such as buckets and jerry cans. We conducted an evaluation to assess both self-reported and observed use over a 6-month period between November 2014 and May 2015. A total of 866 packs were distributed to 618 households in six communities in rural Haiti, and 431 and 441 households were surveyed at midline and end line, respectively. We performed linear regression to assess change of self-reported use over time. Although 79.3% of respondents reported continued use of the 20-L pack after 6 months, other measures of self-reported use were low, with only 16.8% reporting to have used the pack the last time they collected water and 10.3% preferring the pack over other water collection containers. In addition, only 10.2% of all people collecting water at community sources were observed using packs and 12.0% of all households surveyed had water in the pack at the time of visit. Pack use varied by community and demographics. Although women were targeted during distribution, men preferred the pack and were more commonly observed using it at the community water sources. In conclusion, the use of the PackH2O was not widely adopted in rural Haiti; however, further research is needed to assess the pack acceptance in areas where back-loading is more common and in emergency settings.

Feeding of infant formula using contaminated bottles may be an important transmission pathway of enteric pathogens during early life. Determinants of suboptimal bottle hygiene and the feasibility and acceptability of intervention strategies have not been well assessed. We evaluated the extent of bottle contamination, its contributing factors, and options for promoting improved bottle hygiene in a Peruvian shantytown. During Phase 1, we sampled from bottles and caregiver hands (n = 48) and processed for enumeration of total coliform and Escherichia coli colony-forming units. A semi-structured questionnaire captured bottle use and hygiene practices. Phase 2 involved the identification of candidate practices to recommend to caregivers. Phase 3 consisted of a behavioral trial in which 14 caregivers were educated about improved practices for bottle disinfection and later reported on their experiences implementing them. Fecal bacteria were detected in 43.8% of bottles sampled during Phase 1 and in 21.7% of hands. Caregivers overall did not use effective methods for disinfecting bottles, displayed misunderstandings surrounding hygienic practices, and few had ever discussed bottle hygiene with a health provider. Findings from the behavioral trial indicated that the improved practice of brushing the bottle with dish detergent for 30 seconds after every use is preferable to boiling the bottle for several minutes daily as caregivers reported that the brush was simple to use, efficient, and practical. The promotion of a bottle brush and detergent is a feasible and acceptable intervention strategy in peri-urban settings, and future research should evaluate its long-term effectiveness for reducing bottle contamination.

Livestock farming is common in low-income settings as a source of income and animal-sourced food. However, there is growing evidence of the harmful health effects of proximity of animals to infants and young children, especially through exposure to zoonotic pathogens. Poultry ownership is almost universal in rural Burkina Faso. Poultry feces are a significant risk factor for enteric diseases that are associated with child undernutrition. To investigate the extent of exposure to livestock feces among young children and caregivers, we conducted direct observations of 20 caregiver–child dyads for a total of 80 hours (4 hours per dyad) and recorded water quality, sanitation, and hygiene (WASH)-related behaviors. We also undertook in-depth interviews with these caregivers and focus group discussions with separate groups of men and women who were poultry farmers. Poultry and other livestock feces were visible in all 20 and 19 households, respectively, in both kitchen areas and in the household courtyards where children frequently sit or crawl. Direct soil ingestion by young children was observed in almost half of the households (45%). Poor handwashing practices were also common among caregivers and children. Although latrines were available in almost all households, child feces disposal practices were inadequate. This body of research suggests an urgent need to adapt conventional WASH and livestock interventions to reduce the exposure of infants and young children to livestock feces.

In 2012, approximately 5.6 million Zambians did not have access to improved sanitation and around 2.1 million practiced open defecation. The Zambia Sanitation and Hygiene Program (ZSHP), featuring community-led total sanitation, began in November 2011 to increase the use of improved sanitation facilities and adopt positive hygiene practices. Using a pre- and post-design approach with a population-level survey, after 3 years of implementation, we evaluated the impact of ZSHP in randomly selected households in 50 standard enumeration areas (representing 26 of 65 program districts). We interviewed caregivers of children younger than 5 years old (1,204 and 1,170 female caregivers at baseline and end line, respectively) and inspected household toilet facilities and sites for washing hands. At end line, 80% of households had access to improved sanitation facilities versus 64.1% at baseline (prevalence ratio [PR] = 1.25; 95% CI: 1.18–1.31) and 14.1% did not have a toilet facility compared with 19.4% at baseline. At end line, 10.6% of households reported living in an open defecation-free certified village compared with 0.3% at baseline (PR = 32.0; 95% CI: 11.9–86.4). In addition, at end line, 33.4% of households had a specific place for washing hands and 61.4% of caregivers reported handwashing with a washing agent after defecation or before preparing food compared with 21.1% (PR = 1.59; 95% CI: 1.39–1.82) and 55.2% (PR = 1.11; 95% CI: 1.04–1.19) at baseline, respectively. Community-led total sanitation implementation in Zambia led to improvements in access to improved sanitation facilities, reduced open defecation, and better handwashing practices. There is however a need for enhanced investment in sanitation and hygiene promotion.

Latrine access alone may be insufficient to encourage households to dispose of young children’s feces safely in a latrine, and little is known about the determinants of improved child feces disposal. We used longitudinal data collected at up to three timepoints for children less than 5 years of age from households in Odisha, India, which received a combined household-level piped water supply and sanitation intervention, but did not specifically promote the safe disposal of child feces. Among the 85% of intervention households who reported access to improved sanitation, we characterized child defecation and feces disposal practices by age, across time, and season, and assessed determinants of improved disposal. Feces from children less than 3 years of age was commonly picked up by caregivers but disposed of unsafely with garbage into open areas (56.3% of households) or in a drain/ditch (6.2%). Although children 3 and 4 years were more likely to use a latrine than younger children, their feces was also more likely to be left in the open if they did not defecate in a latrine. For children less than 5 years of age, most (84.7%) children’s feces that was safely disposed of in a latrine was because of the children defecating in the latrine directly. Significant predictors for disposing of child feces in an improved latrine were the primary female caregiver reporting using a latrine to defecate, the child’s age, and water observed at place for handwashing. These findings suggest that child feces interventions should focus on encouraging children to begin using a toilet at a younger age and changing the common behavior of disposing of young child’s feces into open areas.

A high probability of another outbreak of communicable disease exists in sub-Saharan African countries, after the Ebola virus disease outbreak of 2014. Thus, health-care facility (HCF) preparedness for a prompt and effective response to disease outbreaks needs to be ascertained. In this study, Nigerian health-care workers’ (HCWs) knowledge of preparedness, perception of the level of preparedness existing in these HCFs, militating factors, and possible ways to improve, were evaluated through qualitative data collection, using focus group discussion and in-depth interview. Among the 193 HCWs which participated in the study, the perception of 190 (98.4%) was that their HCFs were insufficiently equipped to respond to disease outbreaks. None of the facilities had an emergency operation unit (EOU). Most HCWs perceived preparedness as observation of universal precautions. Other aspects of preparedness, such as training, routine emergency drills, disease surveillance, waste management, and design and location of HCFs were minimally mentioned. None of the participants had undergone any form of emergency drill training. Among the suggestions of how to improve on preparedness were immunization of staff, improved inter-departmental communication within the HCF, and routine training. The overall poor level of preparedness which exists in the HCFs means that they cannot prevent or contain a communicable disease outbreak. There is a need to improve universal precautions, communication within the HCFs, and routine interpretation of surveillance data by epidemiologists. There is also a need for the establishment of EOU in every HCF, a system that responds to, and manages emergency response to disease outbreaks, which also must be functional during non-outbreak periods.

Peruvian research output is one of the lowest in South America and is limited to the work of a small group of institutions and related to few subjects, such as infectious diseases. We determined the proportion of subsequent publication and its associated factors of the abstracts with Peruvian affiliation presented to the American Society of Tropical Medicine and Hygiene annual meetings between 2006 and 2010. Approximately 27% (79/296) of abstracts were published within 6 years of presentation, with a median time to publication of 16 months (interquartile range: 9–28). In the adjusted analysis, abstracts with a higher proportion of authors from Peruvian institutions were less likely to be published (risk ratio: 0.5; 95% CI: 0.3–0.8). In conclusion, one of four of the analyzed abstracts was published. Even though this proportion is higher than that in other meetings in Peru and South America, publication rates —especially among Peruvian-only collaborations— still need to be improved.