The American Journal of Tropical Medicine and Hygiene - Current Issue

This article describes similarities and differences in the response of governments and the international community to the current 2019 coronavirus disease (COVID-19) and the 2014 West African Ebola epidemic. It expresses the opinion that the speed and scale of the response to COVID-19 are affected by the important role that China plays in the global economy. By contrast, insufficient and less timely action was initially undertaken in West African countries during the 2014 Ebola epidemic. It concludes by stating why preparedness for and response to all disease outbreaks, also in countries of lower economic importance, should become a priority in the global health agenda.

The optimal time to initiate research on emergencies is before they occur. However, timely initiation of high-quality research may launch during an emergency under the right conditions. These include an appropriate context, clarity in scientific aims, preexisting resources, strong operational and research structures that are facile, and good governance. Here, Nebraskan rapid research efforts early during the 2020 coronavirus disease pandemic, while participating in the first use of U.S. federal quarantine in 50 years, are described from these aspects, as the global experience with this severe emerging infection grew apace. The experience has lessons in purpose, structure, function, and performance of research in any emergency, when facing any threat.

Malaria clinical studies entailing the experimental infection of healthy volunteers with Plasmodium parasites by bites from infected mosquitos, injection of cryopreserved sporozoites, or injection of blood-stage parasites provide valuable information for vaccine and drug development. Success of these studies depends on maintaining safety. In this mini-review, we discuss the safety risks and associated mitigation strategies of these three types of experimental malaria infection. We aimed to inform researchers and regulators who are currently involved in or are planning to establish experimental malaria infection studies in endemic or non-endemic settings.

This case report underlines the appearance of a “walking pneumonia” in a novel coronavirus disease (COVID-19) patient, with evidence of progressive lung involvement on chest imaging studies. The patient traveled from Wuhan, Hubei, China, to Thailand in January 2020. One of her family members was diagnosed with COVID-19. She presented to the hospital because of her concern, but she was without fever or any respiratory symptoms. Three days earlier, her nasopharyngeal and throat swabs revealed a negative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Her initial chest radiography was abnormal, and her first sputum SARS-CoV-2 test yielded inconclusive results. A subsequent sputum test was positive for SARS-CoV-2. Diagnosis in this patient was facilitated by chest imaging and repeat viral testing. Thus, chest imaging studies might enhance capabilities for early diagnosis of COVID-19 pneumonia.

Dengue is the most common mosquito-borne flaviviral infection in the world today. Several factors contribute and act synergistically to cause severe infection. One of these is dysregulated host immunological mediators that cause transient pathophysiology during infection. These mediators act on the endothelium to increase vascular permeability, which leads to plasma leakage compromising hemodynamics and coagulopathy. We conducted a prospective study to explore the expression of pro- and anti-inflammatory cytokines and how they relate to clinical dengue manifestations, by assessing their dynamics through acute dengue infection in adults admitted to the Hospital for Tropical Diseases, Bangkok, Thailand. We performed cytokine analysis at three phases of infection for 96 hospitalized adults together with serotyping of confirmed dengue infection during the outbreaks of 2015 and 2016. The serum concentrations of seven cytokines (interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha, and interferon gamma) were measured in duplicate using a commercial kit (Bio-Plex Human Cytokine Assay). In this study, the cytokine profile was suggestive of a T-helper 2 response. Most patients had secondary infection, and the levels of viremia were higher in patients with plasma leakage than those without plasma leakage. In addition, we observed that bleeding and hepatitis were associated with significantly higher levels of IL-8 during the early phases of infection. Furthermore, IL-6 levels in the early phase of infection were also elevated in bleeding patients with plasma leakage. These results suggest that IL-6 and IL-8 may act in synergy to cause bleeding in patients with plasma leakage.

Four formulations of an investigational tetravalent dengue purified inactivated vaccine, administered as two doses one month (M) apart, were previously shown to be immunogenic and well-tolerated up to M13 of the phase I study NCT01702857. Here, we report results of the follow-up from M14 to year (Y) 3. One hundred healthy Puerto Rican adults, predominantly dengue virus (DENV)–primed, were randomized 1:1:1:1:1 to receive placebo or vaccine formulations: 1 μg/serotype/dose adjuvanted with aluminum, AS01E or AS03B, or aluminum-adjuvanted 4 μg/serotype/dose. No serious adverse events occurred. Two medically-attended potential immune-mediated disease cases, vaccination unrelated, were reported (groups 1 µg+Alum and 1 µg+AS03B). Of 14 instances of suspected dengue, none were laboratory confirmed. Geometric mean neutralizing antibody titers against DENV 1-4 waned from M14, but remained above pre-vaccination levels for DENV 1-3, with the highest values for group 1 µg+AS03B: 1220.1, 920.5, 819.4, and 940.5 (Y2), and 1329.3, 1169.2, 1219.8, and 718.9 (Y3). All formulations appeared to be safe and immunogenic during the 3-year follow-up.

Following the large outbreak of Zika virus in the Western Hemisphere, many infants have been born with congenital Zika virus infection. It is important to describe the functional outcomes seen with congenital infections to allow for their recognition and appropriate interventions. We evaluated 120 children conceived during the 2015–2016 Zika virus outbreak in Paraíba, Brazil, who were approximately 24 months old, to assess functional outcomes. All children met either anthropometric criteria or laboratory criteria suggestive of possible congenital Zika virus infection. We collected results of previous medical evaluations, interviewed parents, and performed physical examinations and functional assessments, for example, the Hammersmith Infant Neurological Examination (HINE). We compared patterns of neurologic outcomes and developmental delay at age 24 months by whether children met anthropometric or laboratory criteria, or both. Among children meeting both criteria, 60% (26/43) were multiply affected (had severe motor impairment, severe developmental delay, and suboptimal HINE scores), compared with 5% (3/57) meeting only laboratory criteria and none (0/20) meeting only anthropometric criteria. Of the remaining 91 children, 49% (45) had developmental delay, with more severe delay seen in children meeting both criteria. Although children meeting physical and laboratory criteria for potential congenital Zika virus infection were more severely affected, we did identify several children with notable adverse neurologic outcomes and developmental delay with no physical findings but potential laboratory evidence of Zika virus infection. Given this, all children who were potentially exposed in utero to Zika virus should be monitored in early childhood for deficits to allow for early intervention.

Two confirmed human cases of Zika virus (ZIKV) were reported in the district of Miri, Sarawak, in 2016. Following that, a mosquito-based ZIKV surveillance study was conducted within 200-m radius from the case houses. Mosquito surveillance was conducted using five different methods, that is, biogents sentinel mosquito (BG) sentinel trap, modified sticky ovitrap, resting catch, larval surveillance, and conventional ovitrap. A total of 527 and 390 mosquito samples were obtained from the case houses in two localities, namely, Kampung Lopeng and Taman Shang Ri La, Miri, Sarawak, respectively. All mosquitoes collected were identified, which consisted of 11 species. Aedes albopictus, both the adult and larval stages, was the dominant species. Resting catch method obtained the highest number of adult mosquitoes (67%), whereas ovitrap showed the highest catch for larval mosquitoes (84%). Zika virus was detected in both adults and larvae of Ae. albopictus together with adults of Culex gelidus, and Culex quinquefasciatus using the real-time reverse transcriptase polymerase chain reaction (PCR) technique. It was noteworthy that Ae. albopictus positive with ZIKV were caught and obtained from four types of collection method. By contrast, Cx. gelidus and Culex quinquefasciatus adults collected from sticky ovitraps were also found positive with ZIKV. This study reveals vital information regarding the potential vectors of ZIKV and the possibility of transovarian transmission of the virus in Malaysia. These findings will be essentials for vector control program managers to devise preparedness and contingency plans of prevention and control of the arboviral disease.

Zika virus, which is transmitted by Aedes aegypti mosquitoes and through sexual transmission, disproportionally affects the human fetus. Guatemala experienced a surge of Zika cases beginning in 2016. We conducted a qualitative study of community perceptions of the seriousness of Zika, as well as the effectiveness, feasibility, and collective efficacy of Zika prevention actions. Free listing elicited the preventive actions salient for 68 participants comprising pregnant women, men with a pregnant partner, and women likely to become pregnant; 12 focus group discussions in a highland and a lowland town explored other concepts through rank orderings of prevention practices depicted on cards. Participants’ initial concern about Zika, based on recent experience with chikungunya and high media coverage, diminished because of its mild symptoms and reduced media coverage. Participants identified more than 32 salient preventive actions, many of which are considered effective by programs. Participants ranked water storage container cleaning and regular unspecified cleaning of the house and its surroundings as highly effective, feasible, and of high collective efficacy; however, the actions lacked the specificity needed to effectively destroy mosquito eggs. Community-level removal of tires and discarded containers had lower collective efficacy than household-level implementation because of the municipal and community cooperation needed. Condom use, although salient for Zika prevention, was hindered by gender roles. The findings indicate space for increasing self-efficacy for condom use among fathers-to-be, abandoning nonspecific terms such as “cleaning” and “standing water,” increasing people’s skills in using bleach as an ovicide, and promoting antenatal care and family planning counseling.

The genitourinary tract was recently identified as a potential site of complications related to the congenital Zika syndrome (CZS). We provide the first report of a series of cryptorchidism cases in 3-year-old children with Zika-related microcephaly who underwent consultations between October 2018 and April 2019 as part of the follow-up of the children cohort of the Microcephaly Epidemic Research Group, Pernambuco, Brazil. Of the 22 males examined, eight (36.4%) presented with cryptorchidism. Among 14 undescended testis cases, 11 (78.6%) could be palpated in the inguinal region. Seven of the eight children had severe microcephaly. Conventional risk factors for cryptorchidism were relatively infrequent in these children. We hypothesize that cryptorchidism is an additional manifestation of CZS present in children with severe microcephaly. As in our cases, for most of the children, the testes were located in the inguinal region, and the possible mechanisms for cryptorchidism were gubernaculum disturbance or cremasteric abnormality.

We tested 700 serum samples collected throughout Panama from 2015 to 2016 for detecting antibodies and RNA of arboviruses. In convalescent specimens, microsphere immunoassay detected an antibody prevalence of 59.3% for dengue virus (DENV) and 30.3% for Zika virus (ZIKV), which included samples that were collected before the Panamanian surveillance system reported the first case of Zika in the country. For acute sera, the most common arbovirus was DENV with 18 positive samples (6%), followed by four (1.3%) of ZIKV and one (0.6%) of chikungunya virus (CHIKV). Our results indicate a change in the chronology of when ZIKV was first detected in Panama and stress the importance of integrating various approaches to enable improved surveillance of both endemic and emerging arboviruses.

Chronic hepatitis B virus (HBV) infection is a major public health problem in China. We evaluated the impact of psychosocial factors (stigma, disclosure, depression, and anxiety) on health-related quality of life (HRQoL) among people living with chronic HBV infection (CHB) in the city of Dalian, Liaoning Province, China. In this hospital-based cross-sectional study, 401 patients living with chronic HBV infection were enrolled as study participants. Study measures included the Beck depression and anxiety inventory, the WHO Quality of Life (WHOQOL-BREF) assessment, the Toronto Chinese HBV Stigma Scale, and disclosure of HBV status to sexual partners. The primary outcome was HRQoL score as measured by the WHOQOL-BREF. A linear regression model was used to examine the association between HRQoL and the potential risk factors including stigma, disclosure, depression, anxiety, and sociodemographic variables. Stigma, disclosure, depression, and anxiety were the covariates of interest. A majority of the participants were females (n = 251, 65.6%), married (81.6%), and had a college or higher degree (32.4%). Depression, anxiety, stigma, and disclosure of HBV infection were associated with low HRQoL in all four domains of the WHOQOL-BREF (physical, psychological, social, and environmental domains) (P < 0.05), when all psychological factors were included in the model separately. Depression was found to be independently associated with low HRQoL in people living with HBV, when all psychological factors were included in the model simultaneously (P < 0.0001). Our data indicate the urgent need for healthcare providers (HCPs) and policy-makers to implement psychological interventions to improve HRQoL among people living with CHB.

There have been various estimates of the prevalence of hepatitis B and C infections in Nigeria. Recent studies have shown the prevalence to be lower than previously reported. The different populations studied might be responsible for this. It is important to have a real population data that would inform the policies to be adopted for eradication. We set out to determine the prevalence, risk factors, and pattern of hepatitis B and C in Benue State, Central Nigeria. Four thousand and five (4,005) subjects, aged 1 year and older, were selected through a multistage random sampling to represent all parts of the state. Trained health workers administered a validated questionnaire. Rapid test kits were standardized and used in determining the prevalence of the respective viruses. Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis C virus (anti-HCV) were found to be positive in 5% and 1%, respectively, of subjects screened. The prevalence varied from one local government area to another, with HBsAg being 8% in the highest to 2% in the lowest LGC, and anti-HCV being 3% in the highest and 0% in the lowest. Age, previous close contact with a patient, and multiple sex partners were the most important risk factors for hepatitis B virus (HBV) infection, whereas age and previous blood transfusion were the most important risk factors for hepatitis C virus (HCV) infection. HBV immunization may be having an impact in reducing the prevalence of the virus. Nigeria appears to be moving from high endemicity to the intermediate one.

HIV-exposed, uninfected (HEU) children are a growing population at particularly high risk of infection-related death in whom preventing diarrhea may significantly reduce under-5 morbidity and mortality in sub-Saharan Africa. A historic cohort (1999–2002) of Kenyan HEU infants followed from birth to 12 months was used. Maternal and infant morbidity were ascertained at monthly clinic visits and unscheduled sick visits. The Andersen–Gill Cox model was used to assess maternal, environmental, and infant correlates of diarrhea, moderate-to-severe diarrhea (MSD; diarrhea with dehydration, dysentery, or related hospital admission), and prolonged/persistent diarrhea (> 7 days) in infants. HIV-exposed, uninfected infants (n = 373) experienced a mean 2.09 (95% CI: 1.93, 2.25) episodes of diarrhea, 0.47 (95% CI: 0.40, 0.55) episodes of MSD, and 0.34 (95% CI: 0.29, 0.42) episodes of prolonged/persistent diarrhea in their first year. Postpartum maternal diarrhea was associated with increased risk of infant diarrhea (Hazard ratio [HR]: 2.09; 95% CI: 1.43, 3.06) and MSD (HR: 2.89; 95% CI: 1.10, 7.59). Maternal antibiotic use was a risk factor for prolonged/persistent diarrhea (HR: 1.63; 95% CI: 1.04, 2.55). Infants living in households with a pit latrine were 1.44 (95% CI: 1.19, 1.74) and 1.49 (95% CI: 1.04, 2.14) times more likely to experience diarrhea and MSD, respectively, relative to those with a flush toilet. Current exclusive breastfeeding was protective against MSD (HR: 0.30; 95% CI: 0.15, 0.58) relative to infants receiving no breast milk. Reductions in maternal diarrhea may result in substantial reductions in diarrhea morbidity among HEU children, in addition to standard diarrhea prevention interventions.

Travelers’ diarrhea (TD) is common among foreign travelers to Thailand. We performed a prospective cohort study to determine the TD incidence among foreign adult travelers to Thailand. We retrieved baseline demographic data, travel plans, and health history on enrolling individuals and collected follow-up questionnaires on days 7, 14, and 28 from the day of arrival. We analyzed data from 349 eligible participants. The mean participants’ age was 32.3 years; 55.4% were men. Most of the participants had visited a travel clinic for vaccinations and counseling after arrival in Thailand. The cumulative incidences of the participants developing TD were 14.0% (49/349), 23.5% (82/349), and 33.0% (115/349) at 7, 14, and 28 days, respectively. The median time to develop TD was 9 days (interquartile range 5–18 days) post-arrival. Of 115 participants with TD, 64.3% (74/115) consulted a physician, 1.7% (2/115) were hospitalized, and 11.3% (13/115) had to change their travel plans. We identified young age, eating street food, and not routinely washing hands after using a toilet as risk factors significantly associated with the incidence of TD using the log-rank test in our survival analysis. Up to one-third of foreign travelers developed diarrhea during the first month, and some cases were severe. Although no highly effective TD prevention method exists, the practice of good personal hygiene and avoidance of food and drinks derived from unsanitary sources are still recommended to reduce the risk of travelers’ TD.

Children who travel internationally to visit friends and relatives (VFRs) are at risk for travel-related illness, but underuse pretravel health services. Although primary care clinics can identify travelers and address pretravel health needs, to date, there are few published reports on effective primary care–based pretravel interventions. We developed a quality improvement initiative to increase traveler identification at a primary care clinic serving families that frequently travel to VFRs. Interventions included a screening question asked at all clinic visits, provider and staff training, travel fliers, and health recommendation sheets for families. Interventions were implemented during 2017 and 2018 peak travel seasons. Travel visit rates and characteristics during the intervention period were compared with pre-intervention baseline periods (April–August, 2015–16). Surveys with providers were conducted to assess disruptiveness of the interventions, and rates of duplicate travel visits were assessed. A total of 738 unique travel events were identified during peak travel seasons from 2015 to 2018, encompassing travel to 29 countries across five continents. Overall, there were 428 unique travel events (3.0% of all clinic visits) during peak seasons 2017–18, compared with 310 unique travel events (2.2% of all clinic visits) during peak seasons 2015–16 (rate ratio 1.34 [95% CI: 1.16–1.56], P < 0.001). None of the 18 healthcare providers or staff surveyed found new travel screening processes to be disruptive or bothersome. Implementation of a primary care–based multimodal travel screening and education initiative was associated with a significantly increased rate of travel visits.

Nomads and labor migrants constitute a vulnerable group beset with high healthcare costs due to lack of health insurance coverage. Their inability to pay for health care constitutes a threat to their well-being and health risk to the host community as they have higher morbidity from diseases and serve as a reservoir of infective agents. This study investigated how nomads and labor migrants pay and cope with necessary healthcare costs. A cross-sectional study was carried out among 323 migrants in four local government areas of Oyo State, which were selected purposively. A pretested semi-structured questionnaire that sought information on respondents’ sociodemographics, healthcare payment methods and coping strategies were employed. Data were analyzed using descriptive statistics and chi-square test to test the association between categorical variables at P ≤ 0.05. The mean age of the respondents was 34.4 ± 1.4 years and 53.2% were farmers. Of the 200 respondents who had used the formal healthcare system, 13 (6.5%) obtained free services via the National Health Insurance Scheme (NHIS) and 187 (93.2%) paid out of pocket for service. Coping with health bills, 115 (62.2%) paid from savings, 34 (18.4%) borrowed money, and 58 (31.4%) sold property. Those with formal education were more likely to pay through NHIS (χ2 = 9.7, P = 0.002). Nomads/migrants in this study have demonstrated the inability to cope with payment of health bills, suggesting the need to look into the policy on healthcare funding/support to migrants and educationally disadvantaged persons. The creation of prepaid pooled payment systems such as social and community health insurance schemes is suggested.

The post-malaria neurological syndrome (PMNS) is an unusual and relatively underreported complication of malaria, which usually occurs after the resolution of acute febrile illness and the patient is free from parasitemia. The clinical spectrum of the PMNS varies from acute-onset cerebellar ataxia to significant encephalopathy with focal deficits resembling acute disseminated encephalomyelitis. Uncommon presentations of PMNS include Guillain–Barre syndrome, postural tremor, or even isolated neuropsychiatric features. Although in a significant proportion of PMNS cases clinical resolution occurs with conservative treatment only, corticosteroids have been used in an attempt to hasten recoveries. Here, we present a case of a 12-year-old girl with acute onset, isolated neuropsychiatric features, following Plasmodium falciparum malaria. Neuroimaging, clinical examination, and cerebrospinal fluid studies were within normal limits. The child recovered completely after treatment with methylprednisolone pulse therapy. This case report illustrates the need for creating awareness about this uncommon complication of malaria. In view of the uncommon complication, early diagnosis and prompt treatment might help in the early resolution of symptoms.

Malaria is the leading cause of morbidity and mortality in Uganda. The role of spatial repellent devices in preventing malaria is controversial. The goal of this study was to evaluate the populations’ acceptability of a newly designed insecticide diffuser. We distributed to three families living in southern Uganda a device commercially available, the VAPE® portable set. This spatial repellent device offers several advantages compared with other traditional products. It is powered by lithium batteries that guarantee 20 days of uninterrupted delivery of insecticide; it contains two insecticides: empenthrin and transfluthrin; and it is simple to use, one switch to turn it “on” and/or “off.” It is odorless, and it can be placed anywhere in the living/sleeping area. People can also carry it outside the house. We planned to evaluate people’s compliance with its usage, its reliability, and its overall costs. We conducted a 5-month survey. We distributed the devices to three households, one device per bedroom. Ten males and 11 females, with a mean age of 26 ± 16 (range 10–51) years, lived in these houses. The compliance with the use of the device and its acceptability were high. No side effects were reported. No individual contracted malaria during the 5-month period. The major obstacle we found was the timely delivery of the devices to the evaluation area and initial compliance with the instructions on how to use the device. Larger randomized studies are needed to clarify whether there is a role for this type of spatial repellent devices in the global efforts to prevent malaria.

Malaria is a major public health problem in West Africa. Previous studies have shown that climate variability significantly affects malaria transmission. The lack of continuous observed weather station data and the absence of surveillance data for malaria over long periods have led to the use of reanalysis data to drive malaria models. In this study, we use the Liverpool Malaria Model (LMM) to simulate spatiotemporal variability of malaria in West Africa using daily rainfall and temperature from the following: Twentieth Century Reanalysis (20th CR), National Center for Environmental Prediction (NCEP), European Centre for Medium-Range Weather Forecasts (ECMWF) Atmospheric Reanalysis of the Twentieth Century (ERA20C), and interim ECMWF Re-Analysis (ERA-Interim). Malaria case data from the national surveillance program in Senegal are used for model validation between 2001 and 2016. The warm temperatures found over the Sahelian fringe of West Africa can lead to high malaria transmission during wet years. The rainfall season peaks in July to September over West Africa and Senegal, and the malaria season lasts from September to November, about 1–2 months after the rainfall peak. The long-term trends exhibit interannual and decadal variabilities. The LMM shows acceptable performance in simulating the spatial distribution of malaria incidence. However, some discrepancies are found. These results are useful for decision-makers who plan public health and control measures in affected West African countries. The study would have substantial implications for directing malaria surveillance activities and health policy. In addition, this malaria modeling framework could lead to the development of an early warning system for malaria in West Africa.

One of the most important problems in controlling malaria is the limited access to effective and accurate diagnosis of malaria parasitemia. In the Democratic Republic of Congo (DRC), malaria is one of the leading causes of morbidity and mortality. The purpose of this study was to assess the prevalence of anemia and the relationship with asymptomatic submicroscopic Plasmodium infection. A cross-sectional study was carried out among 1,088 apparently healthy children aged between 6 and 59 months selected at random in the health zone of Miti Murhesa in South Kivu/DRC. Capillary blood was obtained for hemoglobin (Hb) concentration measurement by Hemocue® Hb 301. Malaria detection was performed by microscopy and the loop-mediated isothermal amplification (LAMP) assay. Anemia was defined as Hb < 11g/dL. We applied the chi-square test for comparisons, and multiple logistic regression was used to identify the risk factors for anemia and submicroscopic Plasmodium infection. The prevalence of anemia was 39.6%, and the prevalence of parasitemia was 15.9% and 34.0% using microscopy and LAMP test, respectively. Submicroscopic Plasmodium infection was found in 22.3% of the children. The independent risk factors for anemia are Plasmodium infection, children younger than 24 months, low middle-upper arm circumference, and history of illness two weeks before. Otherwise, children with submicroscopic malaria infection have a significantly increased risk for anemia, with a need of transfusion. The prevalence of malaria infection was underestimated, when microscopy was used to diagnose malaria. Children with low parasitemia detected by LAMP but not by microscopy showed a significantly increased prevalence of anemia.

Artemether–lumefantrine (AL) is the first-line treatment for uncomplicated Plasmodium falciparum infection in Colombia. To assess AL efficacy for uncomplicated falciparum malaria in Quibdo, Choco, Colombia, we conducted a 28-day therapeutic efficacy study (TES) following the WHO guidelines. From July 2018 to February 2019, febrile patients aged 5–65 years with microscopy-confirmed P. falciparum mono-infection and asexual parasite density of 250–100,000 parasites/µL were enrolled and treated with a supervised 3-day course of AL. The primary endpoint was adequate clinical and parasitological response (ACPR) on day 28. We attempted to use polymerase chain reaction (PCR) genotyping to differentiate reinfection and recrudescence, and conducted genetic testing for antimalarial resistance–associated genes. Eighty-eight patients consented and were enrolled; four were lost to follow-up or missed treatment doses. Therefore, 84 (95.5%) participants reached a valid endpoint: treatment failure or ACPR. No patient remained microscopy positive for malaria on day 3, evidence of delayed parasite clearance and artemisinin resistance. One patient had recurrent infection (12 parasites/µL) on day 28. Uncorrected ACPR rate was 98.8% (83/84) (95% CI: 93.5–100%). The recurrent infection sample did not amplify during molecular testing, giving a PCR-corrected ACPR of 100% (83/83) (95% CI: 95.7–100%). No P. falciparum kelch 13 polymorphisms associated with artemisinin resistance were identified. Our results support high AL efficacy for falciparum malaria in Choco. Because of the time required to conduct TESs in low-endemic settings, it is important to consider complementary alternatives to monitor antimalarial efficacy and resistance.

Laboratory detection of malaria antigens has proved valuable for research and epidemiological purposes. We recently developed a bead-based multiplex antigen assay for pan-Plasmodium and Plasmodium falciparum targets. Here, we report integration of a Plasmodium vivax–specific target to this multiplex panel: P. vivax lactate dehydrogenase (PvLDH). Within the multiplex panel, assay signal for purified PvLDH antigen titrated into the single-digit picogram range. Against a panel of polymerase chain reaction (PCR)-confirmed samples from acute P. vivax infections (n = 36), sensitivity was 91.7% in using PvLDH detection for identifying the presence of parasites. Specificity against a panel of persons with no Plasmodium infection (n = 44) was 100%, and specificity against a panel of PCR-confirmed P. falciparum, Plasmodium malariae, or Plasmodium ovale infections (n = 164) was 90.2%. Addition of this PvLDH capture and detection system into the multiplex antigen panel will now allow for sensitive screening for species identification of both P. falciparum and P. vivax in the laboratory.

Invasion of human erythrocytes by merozoites of Plasmodium knowlesi involves interaction between the P. knowlesi Duffy binding protein alpha region II (PkDBPαII) and Duffy antigen receptor for chemokines (DARCs) on the erythrocytes. Information is scarce on the binding level of PkDBPαII to different Duffy antigens, Fya and Fyb. This study aims to measure the binding level of two genetically distinct PkDBPαII haplotypes to Fy(a+b−) and Fy(a+b+) human erythrocytes using erythrocyte-binding assay. The binding level of PkDBPαII of Peninsular Malaysian and Malaysian Borneon haplotypes to erythrocytes was determined by counting the number of rosettes formed in the assay. Overall, the Peninsular Malaysian haplotype displayed higher binding activity than the Malaysian Borneon haplotype. Both haplotypes exhibit the same preference to Fy(a+b+) compared with Fy(a+b−), hence justifying the vital role of Fyb in the binding to PkDBPαII. Further studies are needed to investigate the P. knowlesi susceptibility on individuals with different Duffy blood groups.

Micro-RNAs (miRNAs) play a crucial role in immune regulation, and a common miRNA-146a polymorphism (rs2910164) increased the odds of falciparum malaria in pregnant African women. Here, we examined whether this association holds true in a different population, that is, 449 mainly male and adult malaria patients and 666 community controls in southwestern India. Plasmodium vivax malaria (67%) predominated over falciparum malaria (11%) and mixed species infections (22%). Overall, 59% of the study participants carried the miRNA-146a polymorphism. However, it was not associated with the odds of malaria, irrespective of parasite species. This underlines the importance of considering the complexities of clinical manifestations of malaria, genetic background, and parasite species when disentangling the role of human genetic variation, including those of miRNAs in malaria.

In recent decades and because of migration, Chagas disease has become a global public health problem. A significant focus has been placed on pregnant women who can transmit the disease to their offspring. Here, we report four cases of women who did not know that they were pregnant while they were being treated with benznidazole. A diagnosis was established according to serology and Trypanosoma cruzi polymerase chain reaction (PCR)–standardized tests. Treatment was discontinued when pregnancy was confirmed, and a thorough follow-up was carried out. Although each case was different, none of the mothers developed health problems during pregnancy, and their newborns were delivered without any teratogenic effects.

Trypanosoma cruzi is a zoonotic protozoan parasite vectored by triatomine insects that are endemic to the Americas, including the southern United States. Surveillance of domestic dogs for T. cruzi exposure allows for the determination of geographic regions of transmission that are relevant for human and animal health. The U.S. Department of Homeland Security (DHS) working dogs provide critical security and detection services across the country, and many train or work in the southern United States, where they are at risk for T. cruzi exposure. We sampled blood from 1,610 working dogs (predominantly Belgian Malinois, German shepherds, and Labrador retrievers) from six task forces (including the Transportation Security Administration, Customs and Border Protection, Secret Service, and more) and two canine training centers across 41 states from 2015 to 2018. Canine sera that were reactive on at least two independent serological assays were considered positive for anti–T.-cruzi antibodies. In addition, up to three independent polymerase chain reaction (PCR) assays were used to detect and type T. cruzi DNA. Overall seroprevalence was 7.5%, and four dogs (0.25%, n = 1,610) had detectable parasite DNA in the blood, comprising parasite discrete taxonomic units (DTUs) TcIV and a coinfection of TcI/TcIV. Dogs that worked within versus outside of the geographic range of established triatomines showed comparable seroprevalence (7.3% and 9.2%, respectively; P = 0.61). Determining the prevalence of T. cruzi in these working dogs and looking at spatially associated risk factors have practical implications for disease risk management and could assist with improved control measures to protect both animal and human health.

Chagas disease, caused by Trypanosoma cruzi, is transmitted by insect vectors, and through transfusions, transplants, insect feces in food, and mother to child during gestation. An estimated 30% of infected persons will develop lifelong, potentially fatal cardiac or digestive complications. Treatment of infants with benznidazole is highly efficacious in eliminating infection. This work evaluates the costs of maternal screening and infant testing and treatment for Chagas disease in the United States, including the cost of commercially available benznidazole. We compare costs of testing and treatment for mothers and infants with the lifetime societal costs without testing and consequent morbidity and mortality due to lack of treatment or late treatment. We constructed a decision-analytic model, using one tree that shows the combined costs for every possible mother–child pairing. Savings per birth in a targeted screening program are $1,314, and with universal screening, $105 per birth. At current screening costs, universal screening results in $420 million in lifetime savings per birth-year cohort. We found that a congenital Chagas screening program in the United States is cost saving for all rates of congenital transmission greater than 0.001% and all levels of maternal prevalence greater than 0.06% compared with no screening program.

Elimination of a disease is the holy grail in global health. The pathology of several neglected tropical diseases (NTDs) such as lymphatic filariasis (LF) makes elimination a reality. However, successful elimination requires that NTD programs be sustainable—the ability to confirm that the disease has been eliminated and the capacity to ensure that it does not return. The WHO’s guidelines on NTDs thoroughly detail how to reach elimination. Notwithstanding, comprehensive guidance regarding contextual and programmatic factors that influence sustainability is lacking. Moreover, a comprehensive NTD sustainability framework that includes these factors is nonexistent. This research aimed to develop a framework that identified the critical programmatic and contextual factors influencing sustainability of NTD elimination programs. The methodology included a literature review and a multiple case study. The literature review had two objectives: the first was to identify unique attributes of NTD elimination programs that should be considered when planning for sustainability and the second was to identify an existing sustainability framework that could be adapted to NTD elimination programs. The literature review resulted in a draft sustainability framework that was then tested, using a multi-case study methodology, on the Kenya National Program for Elimination of Lymphatic Filariasis. The result is the first comprehensive NTD sustainability framework that identifies key contextual and programmatic factors that influence NTD sustainability. This framework is an invaluable resource for practitioners and policy makers alike as many countries start to eliminate NTDs.

Exposure to fecal pathogens contributes to childhood diarrhea and stunting, causing harmful short- and long-term impacts to health. Understanding pathways of child fecal exposure and nutritional deficiencies is critical to informing interventions to reduce stunting. Our aim was to explore determinants of latrine use, disposal of child feces, and perceptions and provisions of a safe and clean child play environment among families with children under two (CU2) years to inform the design of a behavior change intervention to address water, sanitation, and hygiene (WASH), and nutrition behaviors. In 2016, we conducted a mixed-methods formative research in western Kenya. We conducted 29 key informant interviews with community leaders, health workers, and project staff; 18 focus group discussions with caregivers of CU2 years; and 24 semi-structured household observations of feeding, hygiene, and sanitation behaviors. We used the capability, opportunity, motivation, and behavior model as our theoretical framework to map caregiver behavioral determinants. Latrine use barriers were lack of latrines, affordability of lasting materials, and social acceptability of unobserved open defecation. Barriers to safe disposal of child feces were lack of latrines, time associated with safe disposal practices, beliefs that infant feces were not harmful, and not knowing where children had defecated. Primary barriers of clean play environments were associated with creating and maintaining play spaces, and shared human and animal compounds. The immediate cost to practicing behaviors was perceived as greater than the long-term potential benefits. Intervention design must address these barriers and emphasize facilitators to enable optimal WASH behaviors in this context.

The study evaluated the effectiveness of an intervention to improve complementary food hygiene behaviors among child caregivers in rural Malawi. Formative research and intervention development was grounded in the risk, attitude, norms, ability, and self-regulation (RANAS) model and targeted washing hands and kitchen utensils with soap, safe utensil storage, reheating of leftover food, and feeding of children by caregivers. Longitudinal research was applied at baseline and follow-up surveys among 320 caregivers. Determinants of selected behaviors were found, and interventions were developed based on the behavior change techniques aligned with these determinants in the RANAS model. The intervention was delivered over 9 months through group (cluster) meetings and household visits and included demonstrations, games, rewards, and songs. We randomly assigned villages to the control or intervention group. Follow-up results indicated a significant increase in three targeted behaviors (washing kitchen utensils with soap, safe utensil storage, and handwashing with soap) among intervention recipients. Several psychosocial factors differed significantly between the intervention and control groups. Mediation results showed that the intervention had a significant effect on these three targeted behaviors. For handwashing, feelings, others’ behavior in the household, and remembering; for washing kitchen utensils, others’ behavior in the household and difficulty to get enough soap; for safe utensils storage, others’ behavior in the village and remembering mediated the effect of the intervention on the targeted behaviors. The study demonstrated that targeting food hygiene behaviors with a theory-driven behavior change approach using psychosocial factors can improve the behavior of child caregivers in rural Malawi.

Food contamination during weaning and complementary feeding can result in high diarrheal incidence among infants. Caregiver practices are important determinants of exposure to foodborne pathogens, and can therefore play a role in reduction in infant food contamination. Through a qualitative approach, we used the Trials of Improved Practices methodology to design a food hygiene intervention in a low-income settlement of Kisumu city in Kenya. These settlements in Kisumu city host a large portion of the city’s population and are faced with a high diarrheal disease burden. Caregivers were selected if they had a child aged 6–9 months, and together, we codesigned a combination of hardware and messaging components targeting handwashing with soap, hygienic feeding, reheating, and hygienic storage of infant food. Caregivers received up to six engagement visits with the research team. The visits were aimed at improving the designed hardware and messaging components. Results showed that feeding items were easily adopted by caregivers, whereas reheating of food was less observed. Households reportedly improved their food storage and handwashing practices. As a result, the hardware components were further refined and tested among the caregivers. Messaging components spurred the aspirations that caregivers had for their children and acted as reminders of practicing good food hygiene. The outcomes of the codesign process provided valuable insights on the knowledge of caregivers, a delivery approach for implementing the intervention, and further informed a subsequent trial that adopted the designed intervention to target early childhood exposure to enteric pathogens through contaminated food.

Acute respiratory infections cause mortality in young children. We assessed the effects of water, sanitation, hygiene (WASH) and nutritional interventions on childhood ARI. Geographic clusters of pregnant women from rural Bangladesh were randomly assigned to receive 1) chlorinated drinking water and safe storage (W); 2) upgraded sanitation (S); 3) handwashing promotion (H); 4) combined water, sanitation, and handwashing (WSH); 5) nutrition intervention including lipid-based nutrient supplements; 6) combined WSH plus nutrition (WSHN); or 7) no intervention (control). Masking of participants was not possible. Acute respiratory illness was defined as caregiver-reported persistent cough, panting, wheezing, or difficulty breathing in the past 7 days among index children, those born to enrolled women. We assessed outcomes at 12 and 24 months of intervention using intention to treat. Compared with children in the control group (ARI prevalence, P: 8.9%), caregivers of index children reported significantly lower ARI in the water (P: 6.3%, prevalence ratio (PR): 0.71; 95% CI: 0.53, 0.96), sanitation (P: 6.4%, PR: 0.75, 95% CI: 0.58, 0.96), handwashing (P: 6.4%, PR: 0.68, 95% CI: 0.50, 0.93), and the combined WSH+N arms (P: 5.9%, PR: 0.67, 95% CI: 0.50, 0.90). Those in the nutrition (P: 7.4%, PR: 0.84, 95% CI: 0.63, 1.10) or the WSH arm (P: 8.9%, PR: 0.99, 95% CI: 0.76, 1.28) reported similar ARI prevalence compared with control children. Single targeted water, sanitation, and hygiene interventions reduced reported respiratory illness in young children. There was no apparent respiratory health benefit from combining WASH interventions.

Tumor necrosis factor (TNF)-α inhibitors increase susceptibility to tuberculosis, but the effect of biologics on susceptibility to leprosy has not been described. Moreover, biologics may play a role in treating erythema nodosum leprosum (ENL). The objectives of this systematic review were to determine whether the development of clinical leprosy is increased in patients being treated with biologics and to assess the use of biologics in treating leprosy reactions. A systematic literature review was completed of patients with leprosy who received treatment with biologics either before or after a diagnosis of leprosy was confirmed. All studies and case reports were included for qualitative evaluation. The search yielded 10 cases (including one duplicate publication) of leprosy diagnosed after initiation of TNF-α inhibitors and four case reports of refractory ENL successfully treated with infliximab or etanercept. An unpublished case of persistent ENL responsive to infliximab is also presented. These data demonstrate that the use of TNF-α inhibitors may be a risk factor for developing leprosy or reactivating subclinical infections. Leprosy can present with skin lesions and arthritis, so leprosy should be considered in patients presenting with these signs before starting treatment with these agents. Leprosy should be considered in patients who develop worsening eruptions and neurologic symptoms during treatment with TNF-α inhibitors. Finally, TNF-α inhibitors appear effective in some cases of refractory ENL.

Although there has been an increasing incidence of bacteremia caused by extended-spectrum beta-lactamase (ESBL)–producing Enterobacteriaceae (ESBL-E) across South East Asia, there are sparse data from the Lao PDR, where laboratory capacity for antimicrobial resistance surveillance is limited. We, therefore, retrospectively reviewed bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae between 2010 and 2014 at Mahosot Hospital, Vientiane, Lao PDR. Clinical and laboratory data relating to all episodes of ESBL-E bacteremia were reviewed over the 5-year period and compared with non–ESBL-E bacteremia. Blood cultures positive for E. coli or K. pneumoniae were identified retrospectively from laboratory records. Clinical and laboratory data were extracted from research databases and case notes and analyzed using STATA. Between 2010 and 2014, we identified 360 patients with E. coli (n = 249) or K. pneumoniae (n = 111) bacteremia, representing 34.8% of all patients with clinically significant bacteremia. Seventy-two (20%) isolates produced ESBL; E. coli accounted for 15.3% (55/360) and K. pneumoniae for 4.7% (17/360), respectively. The incidence of ESBL-producing E. coli bacteremia rose during the study period. By multiple logistic analysis, reported antibiotic use in the previous week was significantly associated with ESBL positivity (P < 0.001, odds ratio 3.89). Although multiresistant, most ESBL-producing E. coli and K. pneumoniae remained susceptible to meropenem (65/65; 100%) and amikacin (64/65; 98.5%). We demonstrated an alarming increase in the incidence of ESBL-E as a cause of bacteremia in Vientiane during the study period. This has implications for empiric therapy of sepsis in Laos, and ongoing surveillance is essential.