The American Journal of Tropical Medicine and Hygiene - Current Issue

Respiratory cryptosporidiosis is thought to be a rare, end-stage complication of HIV. Few studies have systematically examined the frequency of such infection in adults. Sputum specimens submitted for tuberculosis (TB) testing at Mulago Hospital, Uganda, were anonymously retested for Cryptosporidium using real-time polymerase chain reaction (PCR). Visual confirmation using immunofluorescence confocal microscopy was performed for a subset of PCR-positive samples. Of 824 sputum samples tested, 24 (2.9%) were Cryptosporidium positive. Prevalence in sputum ranged between 0% and 10% in each month of the study and exceeded TB prevalence in some months. In this referral population, respiratory Cryptosporidium prevalence was lower in people with HIV (1.3% versus 4.4% without HIV, P = 0.028) and higher in those with TB (6.8% versus 2.6% without TB, P = 0.086). The weak association between respiratory Cryptosporidium infection and TB persisted after controlling for HIV (odds ratio = 3.2, 95% confidence interval: 0.9, 11.8; P = 0.080). This is the first study to document adult respiratory tract cryptosporidiosis in a referral population with presumed TB. These findings 1) confirm that Cryptosporidium respiratory infection occurs in HIV-negative and -positive adults; 2) suggest there is potential for Cryptosporidium to be disseminated or transmitted by coughing or expectoration; and 3) identify possible synergy between Cryptosporidium and TB in the respiratory tract.

Early diagnosis and treatment is the principal strategy to control visceral leishmaniasis (VL), or kala-azar in East Africa. As VL strikes remote rural, sparsely populated areas, kala-azar care might not be accessed optimally or timely. We conducted a qualitative study to explore access barriers in a longstanding kala-azar endemic area in southern Gadarif, Sudan. Former kala-azar patients or caretakers, community leaders, and health-care providers were purposively sampled and thematic data analysis was used. Our study participants revealed the multitude of difficulties faced when seeking care. The disease is well known in the area, yet misconceptions about causes and transmission persist. The care-seeking itineraries were not always straightforward: “shopping around” for treatments are common, partly linked to difficulties in diagnosing kala-azar. Kala-azar is perceived to be “hiding,” requiring multiple tests and other diseases must be treated first. Negative perceptions on quality of care in the public hospitals prevail, with the unavailability of drugs or staff as the main concern. Delay to seek care remains predominantly linked to economic constraint: albeit treatment is for free, patients have to pay out of pocket for everything else, pushing families further into poverty. Despite increased efforts to tackle the disease over the years, access to quality kala-azar care in this rural Sudanese context remains problematic. The barriers explored in this study are a compelling reminder of the need to boost efforts to address these barriers.

Emerging evidence indicates that migrants from Plasmodium falciparum endemic regions are at risk of delayed presentation of P. falciparum malaria. We report three cases of P. falciparum malaria occurring years after arrival in Europe. All patients were originally from Sub-Saharan Africa. Two subjects had controlled human immunodeficiency virus infection and one was a pregnant woman. We performed a literature review of all published cases of delayed presentation of P. falciparum in migrants and identified 32 additional cases. All cases but one originate from sub-Saharan Africa. There was a median time of 36 months between the last visit to a malaria-endemic country and clinical malaria (range: 3 months to 10 years). Pregnancy was the most frequently reported risk factor (11/35 or 31.4%). Parasitemia was ≤ 0.1% in 38% of cases (11/29 reported), and no death was reported. The underlying possible mechanisms for this delayed presentation in migrants from an endemic area probably include the persistence of submicroscopic parasitemia combined with decaying P. falciparum–specific immunity. Suspicion of P. falciparum delayed malaria should remain high in migrants, mainly from sub-Saharan Africa, even without a recent travel history, especially in those presenting risk factors for impaired parasite clearance or distinct immune responses such as pregnancy and HIV infection. In these patients, new prevention and screening strategies should be studied and blood safety policies adapted.

To study the epidemiological distribution and the incident trends of imported malaria from 2012 to 2016 in Zhejiang Province, southeastern China, we collected data on malaria from the Information System for Parasitic Disease Control and Prevention. A total of 1,003 malaria cases were reported during 2012–2016, and all of these cases were imported. Plasmodium falciparum was the predominant species (76.3%) in Zhejiang Province. The percentage of Plasmodium vivax decreased from 33.6% to 8.1%, whereas the percentage of Plasmodium ovale and Plasmodium malariae increased. Most cases were male (89.8%), mostly in the age group of 21–50 years (82.6%). Businessmen (33.0%), workers (21.0%), farmers (18.8%), and overseas laborers (11.7%) were at high risk. The origin of the largest number of imported cases was Africa (89.5%), followed by Asia (10.0%) and Oceania (0.5%). The time interval from illness onset to confirmation was found to be significantly associated with the complications of patients. Out of 3,461 febrile individuals tested during reactive case detection, 10 malaria-positive individuals were identified. Effective surveillance and response system should be strengthened to prevent the reintroduction of malaria.

Liver dysfunction has long been recognized as a clinical feature of malaria. We have observed delayed elevation in the transaminase portion of liver function tests (LFTs) after treatment in some participants undergoing induced blood stage malaria infection. We sought to determine whether similar LFT elevations occur after naturally acquired infection. We performed a retrospective audit of confirmed cases of Plasmodium falciparum and Plasmodium vivax in Queensland, Australia, from 2006 to 2016. All LFT results from malaria diagnosis until 28 days after diagnosis were collected with demographic and clinical information to describe longitudinal changes. The timing of peak LFT elevations was classified as early (0–3 days), delayed (4–11 days), or late (12–28 days) with respect to the day of diagnosis. Among 861 cases with LFT evaluated, an elevated bilirubin level was identified in 12.4% (N = 107/861), whereas elevated alanine transaminase (ALT) and aspartate transaminase levels were observed in 15.1% (N = 130/861) and 14.8% (N = 127/861) of cases, respectively. All peak bilirubin results occurred in the early period, whereas ALT elevations were biphasic, with elevations in the early and delayed periods, with 35.4% (N = 46/130) of cases delayed. Univariate and paired stepwise logistic regression analyses were performed to investigate factors associated with the incidence and timing of transaminase elevation. A raised ALT level at diagnosis was strongly associated with the timing of transaminase elevation. No other demographic, parasitic, or treatment factors were associated. Liver function test abnormalities are likely an inherent although variable aspect of human malaria, and individual-specific factors may confer susceptibility to hepatocyte injury.

Malarial infections are uncommon in the United States and almost all reported cases stem from recent travelers coming from endemic countries. Cerebral malaria (CM) is a severe form of the disease usually affecting children and individuals with limited immunity. Despite proper management, mortality from CM can reach up to 25%, especially when it is associated with brain edema. Inefficient management of the edema may result in brain herniation and death. Uniform guidelines for management of CM-associated brain edema are lacking. In this report, we present a case of CM with associated severe brain edema that was successfully managed using a unique combination of therapeutic hypothermia, hypertonic saline, mannitol, and hyperventilation along with the antimalarial drugs quinidine and doxycycline. Our use of hypothermia was based on its proven benefit for improving neurological outcomes in post-cardiac arrest patients and previous in vitro research, suggesting its potential inhibitory role on malaria growth.

We assessed the ex vivo/in vitro sensitivity of 54 Malian Plasmodium falciparum isolates to artemisinin for the monitoring of drug resistance in this area. The artemisinin sensitivity of parasites was evaluated using 1) the ex vivo and in vitro parasite recrudescence detection after treatment of the ring stage with 1–200 nM artemisinin for 48 hours and 2) the in vitro parasite recrudescence kinetics assay over 7 days after 6-hour treatment of the ring stage with 700 nM dihydroartemisinin (DHA). In addition, as recommended by the World Health Organization for artemisinin resistance characterization, the ring-stage survival assay (RSA0–3 h) was performed and the parasite isolates were sequenced at the kelch 13 propeller locus. No clinical and molecular evidence of artemisinin resistance was observed. However, these isolates present different phenotypic profiles in response to artemisinin treatments. Despite all RSA0–3 h values less than 1.5%, six out of 46 (13.0%) isolates tested ex vivo and four out of six (66.7%) isolates tested in vitro were able to multiply after 48-hour treatments with 100 nM artemisinin. Moreover, five out of eight isolates tested showed faster parasite recovery after DHA treatment in kinetic assays. The presence of such phenotypes needs to be taken into account in the assessment of the efficacy of artemisinins in Mali. The assays presented here appear as valuable tools for the monitoring of artemisinin sensitivity in the field and thus could help to evaluate the risk of emergence of artemisinin resistance in Africa.

Between 2012 and 2016, over 80% of registered malaria cases in Anhui province were Plasmodium falciparum returned from Africa. However, drug-resistance marker polymorphisms in imported P. falciparum cases have not been assessed. This study looked at the distribution of antimalarial–drug resistance by evaluating K13-propeller, pfmdr1, and pfcrt gene mutations. Fourteen synonymous and 15 nonsynonymous mutations in the K13-propeller gene were detected in samples from nine African countries, yet no candidate and validated K13 resistance mutations were found. The prevalence of pfcrt K76T and pfmdr1 N86Y mutants was 27.7% and 19.9%, respectively. Six different pfcrt genotypes were found, with C72V73M74N75T76 being the most common (89.2%). The pfcrt 76-pfmdr1 86 haplotype combination was evaluated in 173 isolates, and the N86T76 genotype was the most prevalent (50.3%). Notably, the prevalence of the N86Y mutation in Africa marked a decline from 31.0% in 2012 to 8.2% in 2016. Our findings suggest that there is no immediate threat to artemisinin efficacy in imported P. falciparum infections returned from Africa to Anhui province. Nevertheless, pfcrt K76T and pfmdr1 N86Y mutations were modestly prevalent, suggesting the presence of chloroquine resistance in these cases. Accordingly, dihydroartemisinin + piperaquine may be a better choice than artesunate + amodiaquine for the treatment of uncomplicated P. falciparum infections in Anhui province. In addition to, artemether–lumefantrine can be introduced as an alternative measure.

Case reports and pathology series suggest associations of female genital schistosomiasis (Schistosoma haematobium) with infertility and ectopic pregnancy. Differential geographic distribution of infertility is not explained by analyses of known risk factors. In this cross-sectional multilevel semi-ecologic study, interpolated prevalence maps for S. haematobium and Schistosoma mansoni in East Africa were created using data from two open-access Neglected Tropical Diseases Databases. Prevalence was extracted to georeferenced survey sample points for Demographic and Health Surveys for Ethiopia, Kenya, Tanzania, and Uganda for 2000 and 2010. Exploratory spatial analyses showed that infertility was not spatially random and mapped the clustering of infertility and its co-location with schistosomiasis. Multilevel logistic regression analysis demonstrated that women living in high compared with absent S. haematobium locations had significantly higher odds of infertility (2000 odds ratio [OR] = 1.5 [confidence interval95 = 1.3, 1.8]; 2010 OR = 1.2 [1.1, 1.5]). Women in high S. haematobium compared with high S. mansoni locations had significantly higher odds of infertility (2000 OR 1.4 [1.1, 1.9]; 2010 OR 1.4 [1.1, 1.8]). Living in high compared with absent S. mansoni locations did not affect the odds of infertility. Infertility appears to be associated spatially with S. haematobium.

Schistosomiasis is still prevalent in some parts of China. A shift in strategy from morbidity control to elimination has led to great strides in the past several decades. The objective of this study was to explore the spatial and temporal characteristics of schistosomiasis in Anhui, an eastern province of China. In this study, township-based parasitological data were collected from annual cross-sectional surveys during 1997–2010. The kernel k-means method was used to identify spatial clusters of schistosomiasis, and an empirical mode decomposition technique was used to analyze the temporal trend for Schistosoma japonicum in each clustered region. Overall, the prevalence of schistosomiasis remained at a low level except for the resurgence in 2005. According to the Caliński–Harabas index, all the townships were classified into three different clusters (median prevalence: 3.6 per 10,100, 1.8 per 10,000 and 1.7 per 10,000), respectively representing high-, median-, and low-risk clusters. There was an increasing tendency observed for the disease over time. The prevalence increased rapidly from 2003 to 2005, peaked in 2006, and then decreased afterward in the high-risk cluster. A moderate increase was observed in the median-risk cluster from 1998 to 2006, but there was an obvious decreasing tendency in the low-risk cluster after the year 2000. The spatial and temporal patterns of schistosomiasis were nonsynchronous across the three clusters. Disease interventions may be adjusted according to the risk levels of the clusters.

Cirrhosis is the dominant cause of portal hypertension globally but may be overshadowed by hepatosplenic schistosomiasis (HSS) in the tropics. In Zambia, schistosomiasis seroprevalence can reach 88% in endemic areas. Bacterial translocation (BT) drives portal hypertension in cirrhosis contributing to mortality but remains unexplored in HSS. Rifaximin, a non-absorbable antibiotic may reduce BT. We aimed to explore the influence of rifaximin on BT, inflammation, and fibrosis in HSS. In this phase II open-label trial (ISRCTN67590499), 186 patients with HSS in Zambia were evaluated and 85 were randomized to standard care with or without rifaximin for 42 days. Changes in markers of inflammation, BT, and fibrosis were the primary outcomes. BT was measured using plasma 16S rRNA, lipopolysaccharide-binding protein, and lipopolysaccharide, whereas hyaluronan was used to measure fibrosis. Tumor necrosis factor receptor 1 (TNFR1) and soluble cluster of differentiation 14 (sCD14) assessed inflammation. 16S rRNA reduced from baseline (median 146 copies/µL, interquartile range [IQR] 9, 537) to day 42 in the rifaximin group (median 63 copies/µL, IQR 12, 196), P < 0.01. The rise in sCD14 was lower (P < 0.01) in the rifaximin group (median rise 122 ng/mL, IQR-184, 783) than in the non-rifaximin group (median rise 832 ng/mL, IQR 530, 967). TNFR1 decreased (P < 0.01) in the rifaximin group (median -39 ng/mL IQR-306, 563) but increased in the non-rifaximin group (median 166 ng/mL, IQR 3, 337). Other markers remained unaffected. Rifaximin led to a reduction of inflammatory markers and bacterial 16S rRNA which may implicate BT in the inflammation in HSS.

It has been postulated that impaired host immunity due to HIV infection reduces parasite egg excretion. Schistosoma/HIV interactions have also been shown to differ by sex. We hypothesized that egg excretion would vary based on both HIV status and sex. We examined data from more than 1,700 participants in eight studies conducted in northwest Tanzania between 2010 and 2016. Schistosoma infection was defined by circulating anodic antigen (CAA) serum levels ≥ 30 pg/mL and/or egg positivity in either stool by Kato Katz method or urine by filtration. We used multivariable analyses to determine the impact of confounding factors such as sex, age, previous praziquantel treatment, and worm burden as measured by serum CAA level, on the relationship between egg excretion and HIV status. HIV-infected individuals were significantly less likely to excrete schistosome eggs than HIV-uninfected individuals, even after controlling for worm burden and sex (OR = 0.6 [0.4, 0.9], P = 0.005). Furthermore, after controlling for worm burden and HIV status, women had lower odds of egg excretion than men (OR = 0.4 [0.3, 0.5], P < 0.001). Sensitivity of egg microscopy was lower in HIV-infected women than HIV-uninfected men (41% versus 61%, P < 0.001), whereas sensitivity in women remained low in both groups (33% versus 37%, P = 0.664). Our study is the first to report that women with Schistosoma infection excrete fewer eggs than men for a given worm burden, regardless of HIV the status. These findings suggest that guidelines for use of microscopy to diagnose Schistosoma infections in HIV-infected individuals and in women merit reconsideration.

Strongyloides stercoralis is a human parasite that can cause a long-term infection. In immunosuppressed patients, strongyloidiasis may be fatal when there is overwhelming autoinfection resulting in the migration of large numbers of larvae through many organs. Definitive diagnosis is still a challenge, and a combination of symptoms, microscopic identification, and serology test results are often used to arrive at a clinical decision. However, intermittent larval excretion, low parasite burden, and occult infections are challenges with parasitological diagnosis of infection with S. stercoralis. Meanwhile, serologic tests using immunoglobulin G and parasite antigen extract have problems of cross-reactivity with other helminthic infections. Recombinant antigen-based serodiagnosis is a good alternative to overcome the laboratory diagnostic issues. Herein, we report on the isolation of cDNA clone encoding an antigen of potential diagnostic value identified from immunoscreening of a S. stercoralis cDNA library. The translated protein had highest similarity to Strongyloides ratti immunoglobulin-binding protein 1. The recombinant antigen produced, rSs1a, was assessed using western blot and enzyme-linked immunosorbent assay. The latter showed 96% diagnostic sensitivity and 93% specificity; thus, rSs1a has good potential for use in serodiagnosis of human strongyloidiasis.

We report a case of thelaziasis in a 26-year-old female, acquired in Oregon. A total of 14 worms were removed from the patient’s left eye and were morphologically identified as being Thelazia gulosa. Until now, only two species of Thelazia have been implicated in causing human disease, Thelazia callipaeda in Asia and Europe and occasional reports of Thelazia californiensis from the United States of America. Here, we describe a third, previously unreported parasite of humans, T. gulosa (the cattle eyeworm) as an agent of human thelaziasis and the first reported case of human thelaziasis in North America in over two decades.

Over the past 20 years, Thelazia callipaeda (the oriental eyeworm) has become endemic in Europe, infecting domestic and wild carnivores and humans. The vector of this nematode, the fruit fly Phortica variegata, has recently been discovered in the United States, and its vector competence is demonstrated for T. callipaeda in this article, therefore representing a potential new threat for infection of carnivores and humans in the United States.

As part of lymphatic filariasis (LF) transmission assessment surveys (TAS) on Fiji, an island-wide assessment of gastrointestinal protozoan infection was performed by inspection of a concomitant stool sample collection to investigate the distribution of parasitic protozoa. All grade 1 and 2 students of 69 schools on the two main islands were targeted in two phases (one in the Western Division and the other in the Central and Northern Divisions, except Taveuni sub-Division of Northern), where fecal samples of 1,800 students were available for coproscopy using formalin-ether-acetate concentration. The overall prevalence of Giardia infection was 1.6%, having 2.2% in Western and 0.8% in Central/Northern Divisions (P = 0.094). The school-level prevalence of giardiasis ranged from 0% to 15.4%, and hotspot analysis using the Getis-Ord Gi* method detected spatial heterogeneity of giardiasis prevalence in schools around Lautoka (Z-score = 3.36, P value < 0.05), an area affected by Cyclone Kofi in February 2014. Any protozoan infection prevalence was 4.9% in Western and 4.4% in Central/Northern Divisions (P = 0.825). Real-time polymerase chain reaction analysis to confirm the findings from a parasitological examination of a 10% stool archive in 95% ethanol from Western Division revealed an elevated prevalence of giardiasis up to 22.4%, the presence of Entamoeba histolytica, and the absence of Cryptosporidium parvum. Obtaining stool samples alongside LF TAS is a convenient access platform for cosurveillance of gastrointestinal protozoan infection and has pinpointed hitherto unknown hotspots of giardiasis in urban city centers of Fiji. This calls for greater attention to apply tailored water, sanitation and hygiene measures for the control of these parasites.

Although the high case fatality rate (CFR) associated with Ebola virus disease (EVD) is well documented, there are limited data on the actual modes of death. We conducted a retrospective, observational cohort study among patients with laboratory-confirmed EVD. The patients were all seen at the Eternal Love Winning Africa Ebola Treatment Unit in Monrovia, Liberia, from June to August 2014. Our primary objective was to describe the modes of death of our patients and to determine predictors of mortality. Data were available for 53 patients with laboratory-confirmed EVD, with a median age of 35 years. The most frequent presenting symptoms were weakness (91%), fever (81%), and diarrhea (78%). Visible hemorrhage was noted in 25% of the cases. The CFR was 79%. Odds of death were higher in patients with diarrhea (odds ratio = 26.1, P < 0.01). All patients with hemorrhagic signs died (P < 0.01). Among the 18 fatal cases for which clinical information was available, three distinct modes of death were observed: sudden death after a moderate disease process (44%), profuse hemorrhage (33%), and encephalopathy (22%). We found that these modes of death varied by age (P = 0.04), maximum temperature (P = 0.43), heart rate on admission (P = 0.04), time to death from symptom onset (P = 0.13), and duration of hospitalization (P = 0.04). Although further study is required, our findings provide a foundation for developing treatment strategies that factor in patients with specific disease phenotypes (which often require the use of aggressive hydration). These findings provide insights into underlying pathogenic mechanisms resulting in severe EVD and suggest direction for future research and development of effective treatment options.

Heartland virus (HRTV) is a phlebovirus suspected to be transmitted by Amblyomma americanum, commonly known as the lone star tick, and reported to cause illness in humans, which is characterized by thrombocytopenia and leukopenia. Heartland virus–reactive antibodies have been detected in a variety of wildlife species including white-tailed deer (WTD). To better understand the potential role of deer in the epidemiology of HRTV, we experimentally inoculated five WTD fawns with HRTV and monitored for clinical disease, viremia, virus shedding, and seroconversion. None of the animals showed signs of clinical disease, and there was no detectable viremia or virus shedding postinoculation. Two wild-caught fawns entered the study with preexisting antibody titers against HRTV. All animals showed minimal immune responses against HRTV after needle inoculation. In conclusion, this study does not indicate that WTD are a likely reservoir for HRTV in natural settings.

Two rotavirus vaccines, RotaTeq and Rotarix, are licensed for global use; however, the protection they confer to unvaccinated individuals through indirect effects remains unknown. We systematically reviewed the literature and quantified indirect rotavirus vaccine effectiveness (VE) for preventing rotavirus hospitalization in children aged less than 5 years. From 148 identified abstracts, 14 studies met our eligibility criteria. In our main analysis using a random-effects model, indirect rotavirus VE was 48% (95% confidence interval [CI]: 39–55%). In a subgroup analysis by country income level, indirect VE was greater in high-income countries (52%; 95% CI: 43–60%) than in low- and middle-income countries (LMICs) (25%; 95% CI: 5–41%). In a sensitivity analysis using a quality-effects model, the indirect VE in LMICs was not statistically significant (25%; 95% CI: 0–44%). Our findings highlight the importance of increasing rotavirus vaccine coverage, particularly in LMICs where evidence for indirect VE is limited and rotavirus burden is high.

Dengue transmission in Mexico has become a major public health problem. Few epidemiological studies have examined the seroprevalence of dengue in Mexico, and recent estimates are needed to better understand dengue transmission dynamics. We conducted a dengue seroprevalence survey among 1,668 individuals including all age groups in three urban settings in Yucatan, Mexico. Children (< 19 years old) were selected randomly from schools. The adults (≥ 19 years old) were selected from healthcare facilities. Participants were asked to provide a venous blood sample and to answer a brief questionnaire with demographic information. Previous exposure to dengue was determined using indirect immunoglobulin G enzyme-linked immunosorbent assay. The overall seroprevalence was 73.6%. The age-specific seroprevalence increased with age, going from 51.4% (95% confidence interval [CI] = 45.0–57.9%) in children ≤ 8 years to 72% (95% CI = 66.3–77.2%) in the 9- to 14-years old. The highest seroprevalence was 83.4% (95% CI = 77–82.2%) in adults greater than 50 years. The seroprevalence in Merida was 68.6% (95% CI = 65–72%), in Progreso 68.7% (95% CI = 64.2–72.8%), and in Ticul 85.3% (95% CI = 81.9–88.3%). Ticul had the highest seroprevalence in all age groups. Logistic regression analysis showed that age and city of residence were associated with greater risk of prior dengue exposure. The results highlight the level of past exposure to dengue virus including young children. Similar studies should be conducted elsewhere in Mexico and other endemic countries to better understand the transmission dynamics of dengue.