The American Journal of Tropical Medicine and Hygiene - Current Issue

The International Committee on Taxonomy of Viruses (ICTV) has implemented numerous changes to the taxonomic classification of bunyaviruses over the years. Whereas most changes have been justified and necessary because of the need to accommodate newly discovered and unclassified viruses, other changes are a cause of concern, especially the decision to demote scores of formerly recognized species to essentially strains of newly designated species. This practice was first described in the seventh taxonomy report of the ICTV and has continued in all subsequent reports. In some instances, viruses that share less than 75% nucleotide sequence identity across their genomes, produce vastly different clinical presentations, possess distinct vector and host associations, have different biosafety recommendations, and occur in nonoverlapping geographic regions are classified as strains of the same species. Complicating the matter is the fact that virus strains have been completely eliminated from ICTV reports; thus, critically important information on virus identities and their associated biological and epidemiological features cannot be readily related to the ICTV classification. Here, we summarize the current status of bunyavirus taxonomy and discuss the adverse consequences associated with the reclassification and resulting omission of numerous viruses of public health importance from ICTV reports. As members of the American Committee on Arthropod-borne Viruses, we encourage the ICTV Bunyavirus Study Group to reconsider their stance on bunyavirus taxonomy, to revise the criteria currently used for species demarcation, and to list additional strains of public and veterinary importance.

Important strides have been made within the past decade toward malaria elimination in many regions, and with this progress, the feasibility of eradication is once again under discussion. If the ambitious goal of eradication is to be achieved by 2040, all species of Plasmodium infecting humans will need to be targeted with evidence-based and concerted interventions. In this perspective, the potential barriers to achieving global malaria elimination are discussed with respect to the related diversities in host, parasite, and vector populations. We argue that control strategies need to be reorientated from a sequential attack on each species, dominated by Plasmodium falciparum to one that targets all species in parallel. A set of research themes is proposed to mitigate the potential setbacks on the pathway to a malaria-free world.

Uninsured and unprepared travelers to countries with endemic tropical diseases pose great health-care burdens and financial risks on returning to the United States. We discuss the delayed presentation of an uninsured U.S. traveler returning from West Africa with severe malaria who required intensive care measures to save his life. Despite being critically ill on his return, he sat rigoring on his couch taking antipyretics for 3 days, while he applied for insurance on the Affordable Care Act website and waited for approval because he was fearful of the costs of seeking care. He also had limited access to affordable pretravel consultation and prophylactic medications and did not take them because he had no insurance. Average fees for a malaria hospitalization cost $25,789; however, this patient accumulated fees nearing $300,000—and his care was reimbursed by emergency Medicaid with $39,000, because his newly accepted insurance did not cover his hospitalization. This patients’ experience in the U.S. health-care system with a deadly tropical disease exemplifies the need for affordable universal coverage of pretravel consultation and malaria prophylaxis. In this uncertain political time and the recent removal of the health insurance mandate, along with the White House and Congress wanting to reform health care, this case supports the American Society of Tropical Medicine and Hygiene (ASTMH) statements showing the need for funding of tropical medicine education, research, and public health services for travelers, not cuts to important agencies and insurances that keep our country safe from imported deadly tropical diseases.

In the Peruvian North Coast (PNC), the number of Plasmodium vivax malaria cases increased steadily from 2007 to 2010 despite a significant decline in the overall number of cases in Peru during the same period. To better understand the transmission dynamics of P. vivax populations in the PNC and the neighboring Ecuadorian Amazon Basin (EAB), we studied the genetic variability and population structure of P. vivax in these areas. One hundred and twenty P. vivax isolates (58 from Piura and 37 from Tumbes in the PNC collected from 2008 to 2010 and 25 from the EAB collected in Pastaza from 2001 to 2004) were assessed by five polymorphic microsatellite markers. Genetic variability was determined by expected heterozygosity (He) and population structure by Bayesian inference cluster analysis. We found very low genetic diversity in the PNC (He = 0–0.32) but high genetic diversity in the EAB (He = 0.43–0.70). Population structure analysis revealed three distinct populations in the three locations. Six of 37 (16%) isolates from Tumbes had an identical haplotype to that found in Piura, suggesting unidirectional flow from Piura to Tumbes. In addition, one haplotype from Tumbes showed similarity to a haplotype found in Pastaza, suggesting that this could be an imported case from EAB. These findings strongly suggest a minimal population flow and different levels of genetic variability between these two areas divided by the Andes Mountains. This work presents molecular markers that could be used to increase our understanding of regional malaria transmission dynamics, which has implications for the development of strategies for P. vivax control.

A decade after the Global Malaria Eradication Program, El Salvador had the highest burden of malaria in Mesoamerica, with approximately 20% due to Plasmodium falciparum. A resurgence of malaria in the 1970s led El Salvador to alter its national malaria control strategy. By 1995, El Salvador recorded its last autochthonous P. falciparum case with fewer than 20 Plasmodium vivax cases annually since 2011. By contrast, its immediate neighbors continue to have the highest incidences of malaria in the region. We reviewed and evaluated the policies and interventions implemented by the Salvadoran National Malaria Program that likely contributed to this progress toward malaria elimination. Decentralization of the malaria program, early regional stratification by risk, and data-driven stratum-specific actions resulted in the timely and targeted allocation of resources for vector control, surveillance, case detection, and treatment. Weekly reporting by health workers and volunteer collaborators—distributed throughout the country by strata and informed via the national surveillance system—enabled local malaria teams to provide rapid, adaptive, and focalized program actions. Sustained investments in surveillance and response have led to a dramatic reduction in local transmission, with most current malaria cases in El Salvador due to importation from neighboring countries. Additional support for systematic elimination efforts in neighboring countries would benefit the region and may be needed for El Salvador to achieve and maintain malaria elimination. El Salvador’s experience provides a relevant case study that can guide the application of similar strategies in other countries committed to malaria elimination.

Reticulocyte-binding homologues (RH) are a ligand family that mediates merozoite invasion of erythrocytes in Plasmodium falciparum. Among the five members of this family identified so far, only P. falciparum reticulocyte–binding homologue-5 (PfRH5) has been found to be essential for parasite survival across strains that differ in virulence and route of host-cell invasion. Based on its essential role in invasion and early evidence of sequence conservation, PfRH5 has been prioritized for development as a vaccine candidate. However, little is known about the extent of genetic variability of RH5 in the field and the potential impact of such diversity on clinical outcomes or on vaccine evasion. Samples collected during a prospective cohort study of malaria incidence conducted in Kalifabougou, in southwestern Mali, were used to estimate genetic diversity, measure haplotype prevalence, and assess the within-host dynamics of PfRH5 variants over time and in relation to clinical malaria. A total of 10 nonsynonymous polymorphic sites were identified in the Pfrh5 gene, resulting in 13 haplotypes encoding unique protein variants. Four of these variants have not been previously observed. Plasmodium falciparum reticulocyte–binding homologue-5 had low amino acid haplotype (h = 0.58) and nucleotide (π = 0.00061) diversity. By contrast to other leading blood-stage malaria vaccine candidate antigens, amino acid differences were not associated with changes in the risk of febrile malaria in consecutive infections. Conserved B- and T-cell epitopes were identified. These results support the prioritization of PfRH5 for possible inclusion in a broadly cross-protective vaccine.

Babesia is a tick-borne intraerythrocytic parasite that is clinically and diagnostically similar to malaria parasite, conferring risk of misdiagnosis in areas where both parasites are endemic. Data on Babesia in humans in Africa are lacking, despite evidence that it is present in regional animal populations. Samples that were collected in November 2014 to July 2015 in Kilosa district, Tanzania, were evaluated for evidence of malaria and Babesia infection. Clinical data and laboratory samples (i.e., hemoglobin, rapid diagnostic testing [RDT] for malaria, peripheral blood smear, and dried blood spots) from a routine survey were available for analysis. Dried blood spots were tested using an investigational enzyme linked immunosorbent assay (ELISA) against Babesia microti. A total of 1,030 children aged 1 month to < 5 years were evaluated; 186 (18.1%) were malaria RDT positive, 180 (96.8%) of whom had peripheral smears reviewed; 70/180 (38.9%) were smear positive for parasites. The median (inter quartile range) and range of B. microti ELISA signal to cutoff (S/C) ratio was 0.10 (0.06–0.15) and 0.01–1.65, respectively; the S/C ratios were significantly higher in subjects ≥ 1 year as compared with those < 1 year old (P < 0.001). There was also a statistically significant association between a positive RDT for malaria and the Babesia S/C (median 0.09 versus 0.13 in RDT negative versus RDT positive, respectively; P < 0.001). The highest S/C ratios were disproportionately clustered in a few hamlets. The findings suggest that Babesia may be present in Kilosa district, Tanzania. However, serological cross-reactivity and false positivity, notably between Babesia and Plasmodium spp., cannot be definitively excluded and have implications for testing in other settings.

Plasmodium falciparum gametocytes develop over 9–12 days while sequestered in deep tissues. On emergence into the bloodstream, they circulate for varied amounts of time during which certain host factors might influence their further development. We aimed to evaluate the potential association of patient clinical parameters with gametocyte development and carriage via in vivo methods. Seventy-two patients were enrolled from three hospitals in the Volta region of Ghana in 2016. Clinical parameters were documented for all patients, and gametocyte prevalence by microscopy was estimated at 12.5%. By measuring RNA transcripts representing two distinct gametocyte developmental stages using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), we obtained a more precise estimate of gametocyte carriage while also inferring gametocyte maturation. Fifty-three percent of the study participants harbored parasites expressing transcripts of the immature gametocyte-specific gene (PF3D7_1477700), whereas 36% harbored PF3D7_1438800 RNA-positive parasites, which is enriched in mid and mature gametocytes, suggesting the presence of more immature stages. Linear logistic regression showed that patients older than 5 years but less than 16 years were more likely to carry gametocytes expressing both PF3D7_1477700 and PF3D7_1438800 compared with younger participants, and gametocytemia was more likely in mildly anemic individuals compared with those with severe/moderate anemia. These data provide further evidence that a greater number of malaria patients harbor gametocytes than typically estimated by microscopy and suggest a possible association between age, fever, anemia, and gametocytemia.

The pharmacokinetics (PK) and ex vivo activity (pharmacodynamics [PD]) of two artemisinin combination therapies (ACTs) (artemisinin–piperaquine [ARN–PPQ] [Artequick®] and artesunate–amodiaquine [ARS–AQ] [Coarsucam™]) in healthy Vietnamese volunteers were compared following 3-day courses of the ACTs for the preselection of the drugs for falciparum malaria therapy. For PK analysis, serial plasma samples were collected from two separate groups of 22 volunteers after ACT administration. Of these volunteers, ex vivo activity was assessed in plasma samples from seven volunteers who received both ACTs. The area under the concentration–time curve (AUC0–∞) was 3.6-fold higher for dihydroartemisinin (active metabolite of ARS) than that for ARN, whereas the AUC0–∞ of desethylamodiaquine (active metabolite of AQ) was 2.0-fold lower than that of PPQ. Based on the 50% inhibitory dilution values of the volunteers’ plasma samples collected from 0.25 to 3 hours after the last dose, the ex vivo activity of ARS–AQ was 2.9- to 16.2-fold more potent than that of ARN–PPQ against the drug-sensitive D6 Plasmodium falciparum line. In addition, at 1.5, 4.0, and 24 hours after the last dose, the ex vivo activity of ARS–AQ was 20.8-, 3.5-, and 8.5-fold more potent than that of ARN–PPQ against the ARN-sensitive MRA1239 line. By contrast, at 1.5 hours, the ex vivo activity of ARS–AQ was 5.4-fold more active than that of ARN–PPQ but had similar activities at 4 and 24 hours against the ARN-resistant MRA1240 line. The PK–PD data suggest that ARS–AQ possesses superior antimalarial activity than that of ARN–PPQ and would be the preferred ACT for further in vivo efficacy testing in multidrug-resistant falciparum malaria areas.

We measured the prevalence of malaria in pregnancy and estimated its impact on birth weight and length and maternal hemoglobin in 1,180 women from Juruá Valley, the main malaria hotspot in Brazil. Antenatal malaria episodes, 74.6% of them due to Plasmodium vivax, were microscopically diagnosed in 8.0% of the women and were associated with an average reduction in birth weight z-scores of 0.35 (95% confidence interval [CI] = 0.14–0.57) and in birth length z-scores of 0.31 (95% CI = 0.08–0.54), compared with malaria-free pregnancies. Affected mothers had a mean decrease in hemoglobin concentration at delivery of 0.33 g/100 mL (95% CI = 0.05–0.62 g/100 mL); 51.6% were anemic. The timing and frequency of antenatal infections influenced pregnancy outcomes and first- or second-trimester infections were not associated with decreased birth weight and length and maternal hemoglobin at delivery. Although repeated antenatal vivax infections were associated with poorer birth outcomes, even a single vivax malaria episode was associated with a significant reduction in birth weight and length and maternal hemoglobin. Overall, 7.5% women had the parasite’s DNA found in peripheral blood at delivery. Most (83.1%) of these 89 perinatal infections were due to P. vivax and only 7.9% of them progressed to symptomatic disease after delivery. Plasmodium vivax and Plasmodium falciparum DNA was found in 0.6% and 0.3% of 637 cord blood samples examined, respectively, but only one newborn developed clinical neonatal malaria. Our results further challenge the notion that vivax malaria is relatively benign during pregnancy and call for better strategies for its prevention.

Genotyping of allelic variants of Plasmodium falciparum merozoite surface proteins 1 and 2 (msp-1 and msp-2), and the glutamate-rich protein is the gold standard for distinguishing reinfections from recrudescences in antimalarial drug trials. We compared performance of the recently developed 24-single-nucleotide polymorphism (SNP) Barcoding Assay against msp-1 and msp-2 genotyping in a cluster-randomized effectiveness trial of artemether–lumefantrine and dihydroartemisinin–piperaquine in Malawi. Rates of recrudescence and reinfection estimated by the two methods did not differ significantly (Fisher’s exact test; P = 0.887 and P = 0.768, respectively). There was a strong agreement between the two methods in predicting treatment outcomes and resolving the genetic complexity of malaria infections in this setting. These results support the use of this SNP assay as an alternative method for correcting antimalarial efficacy/effectiveness data.

The Triatominae subfamily is composed of 153 hematophagous species that are potential vectors of Trypanosoma cruzi, the etiological agent of Chagas disease. Karyotypic studies in triatomines were initiated in 1909. There are 92 karyotypes described, all grouped into the tribes Rhodniini and Triatomini. Recently, a phylogenetic study of the triatomines that combines molecular data with geological changes was performed. We now discuss how the karyotype evolved with the diversification of the triatomines.

Microsporidia are protists close to the kingdom of fungi that may cause eye infections. Most cases are reported in Asia and affect both immunocompromised and immunocompetent patients. Here, we report a rare case of microsporidial keratoconjunctivitis in an immunocompetent French patient 3 weeks after returning from India. In our patient, Weber trichrome staining of conjunctival scrapings revealed rounded elements approximately 1–3 μm in size. Conventional polymerase chain reaction analysis by ribosomal RNA subunit sequencing showed 100% identity with Vittaforma corneae. Treatment by corneal debridement combined with fluoroquinolone eye drops allowed complete resolution of the lesions. Although rare, ocular microsporidiosis should be investigated in a patient who is native to Asia or has returned from an endemic area and presents with keratoconjunctivitis of undetermined etiology.

Schistosomiasis due to Schistosoma haematobium is a widespread disease usually affecting the urinary tract associated with hematuria and kidney disorders. Neurological damage is rarely reported and symptoms are nonspecific and may suggest brain tumors such as glioma. We describe the first double ectopic haematobium schistosomiasis case involving the brain and intestine.

Cystic echinococcosis (CE) is a globally endemic zoonosis caused by the larval stage of the Echinococcus granulosus sensu lato (s.l.) complex. Although the disease is known to be highly prevalent in certain parts of North and East Africa, data on CE, both in humans and definitive hosts, are extremely scarce for Central Africa. The present study assessed the epidemiology of CE in humans and dogs in rural Gabon. An ultrasound and serologic survey was conducted in volunteers from rural villages in Gabon. A two-step approach was used for serological testing with an indirect hemagglutination assay as a screening test and Western Blot as a confirmatory test. Fecal dog samples were analyzed microscopically, and polymerase chain reaction (PCR) amplification of nad1 and cox1 genes was performed when taeniid eggs were visible. Regional hospitals and the national reference center for parasitology in Gabon were contacted for information about previous cases of CE. Randomly selected communities were invited to participate. Three hundred and forty-eight human volunteers from these communities were screened. No suspected cases of CE were detected. Definitive host screening was performed from 128 fecal samples from representative subregions, but no eggs from E. granulosus s.l. were found. No documented cases of echinococcosis were reported from the local health-care institutions and the national diagnostic reference center in Gabon. Cystic echinococcosis seems to be very rare or absent in Gabon. The reason for this lack of evidence for echinococcosis is unknown, but the absence of livestock may play a major role.

Bancroftian filariasis can cause genital abnormalities related to chronic inflammation and obstruction of the afferent lymphatic vessels, and may demonstrate a “filarial dance sign” on scrotal ultrasound with mobile echogenic particles observed. We present a patient with a positive “filarial dance sign,” travel within Latin America, and negative filarial serology.

Lymphatic filariasis is a mosquito-borne parasitic infection caused by Wuchereria bancrofti and Brugia spp. Commonly seen in tropical developing countries, lymphatic filariasis occurs when adult worms deposit in and obstruct lymphatics. Although not endemic to the United States, a few cases of lymphatic filariasis caused by zoonotic Brugia spp. have been reported. Here we present a case of an 11-year-old female with no travel history who was seen in our clinic for a 1-year history of painless left cervical lymphadenopathy secondary to lymphatic filariasis. We review the literature of this infection and discuss the management of our patient. Using the National Inpatient Sample (NIS), the largest publicly available all-payer inpatient care database in the United States, we also examine the demographics of this infection. Our results show that chronic lymphadenopathy in the head and neck is the most common presenting symptoms of domestic lymphatic filariasis. Diagnosis is often made after surgical lymph node excision. Examination of the NIS from 2000 to 2014 revealed 865 patients admitted with a diagnosis of lymphatic filariasis. Most patients are in the mid to late sixties and are located on the eastern seaboard. Eight hundred and twenty six cases (95.5%) were likely due to zoonotic Brugia spp. and 39 (4.5%) due to W. bancrofti. Despite being rare, these data highlight the need to consider filariasis in patients presenting with chronic lymphadenopathy in the United States.

Loiasis is a vector-borne parasitic disease caused by the filarial nematode Loa loa and transmitted by the tabanid vectors from the genus Chrysops. Loa loa infection is associated with clinical manifestations such as pruritus, migratory transient edema, passage of adult worm in the bulbar conjunctiva, retinal damage, glomerular damage, albuminuria, pleural effusion, hydrocele, and endomyocardial fibrosis. Data reporting the occurrence of spontaneous encephalopathy associated with loiasis are very scanty. Severe adverse events occurring post-ivermectin administered in the framework of the fight against onchocerciasis and/or lymphatic filariasis in loiasis co-endemic areas have been closely associated with very high L. loa microfilariaemia. Different regimens have been used to lower L. loa microfilariaemia before definitive treatment, and many discrepancies have been reported. We report the case of a patient who was admitted to a health facility and hospitalized for 34 days for altered consciousness, blurred vision, headache, and chills. After other potential diagnoses were eliminated, the patient was confirmed with encephalopathy due to loiasis and referred to the Centre for Research on Filariasis and other Tropical Diseases (CRFilMT). On admission at CRFilMT, the patient was harboring 28,700 microfilariae per milliliter of blood (mf/mL), and after four 21-day courses of 400 mg daily albendazole, the L. loa microfilariaemia lowered to 5,060 mf/mL. The patient was then treated with ivermectin 3 mg and a total clearance of microfilariae was observed, with satisfactory clinical evolution and no adverse event. This case study further confirmed that albendazole is effective against L. loa, but might necessitate a longer course.

Ivermectin treatment can cause central nervous system adverse events (CNS-AEs) in persons with very high-density Loa loa microfilaremia (≥ 30,000 mf/mL blood). Hypoendemic onchocerciasis areas where L. loa is endemic have been excluded from ivermectin mass drug administration programs (MDA) because of the concern for CNS AEs. The rapid assessment procedure for L. loa (RAPLOA) is a questionnaire survey to assess history of eye worm. If ≥ 40% of respondents report eye worm, this correlates with ≥ 2% prevalence of very high-density loiasis microfilaremia, posing an unacceptable risk of CNS-AEs after MDA. In 2016, we conducted a L. loa study in 110 ivermectin-naïve, suspected onchocerciasis hypoendemic villages in southern Nigeria. In previous RAPLOA surveys these villages had prevalences between 10% and 67%. We examined 10,605 residents using the LoaScope, a cell phone–based imaging device for rapidly determining the microfilaria (mf) density of L. loa infections. The mean L. loa village mf prevalence was 6.3% (range 0–29%) and the mean individual mf count among positives was 326 mf/mL. The maximum individual mf count was only 11,429 mf/mL, and among 2,748 persons sampled from the 28 villages with ≥ 40% RAPLOA, the ≥ 2% threshold of very high Loa mf density could be excluded with high statistical confidence (P < 0.01). These findings indicate that ivermectin MDA can be delivered in this area with extremely low risk of L. loa–related CNS-AEs. We also concluded that in Nigeria the RAPLOA survey methodology is not predictive of ≥ 2% prevalence of very high-density L. loa microfilaremia.

Chromoblastomycosis is a worldwide chronic subcutaneous infection caused by dematiaceous fungi and clinically characterized by verrucous lesions. Herein, we report a rare case of chromoblastomycosis caused by Fonsecaea monophora in a 60-year-old male carpenter with a 40-year history of psoriasis from Shandong in northern China. A fungal infection coexisting with psoriasis presents a management dilemma. Our patient responded well to combined itraconazole and acitretin therapy and the lesions resolved completely after 1 month of treatment.

Leptospirosis is a potentially fatal emerging zoonosis with worldwide distribution and a broad range of clinical presentations and exposure risks. It typically affects vulnerable populations in (sub)tropical countries but is increasingly reported in travelers as well. Diagnostic methods are cumbersome and require further improvement. Here, we describe leptospirosis among travelers presenting to the GeoSentinel Global Surveillance Network. We performed a descriptive analysis of leptospirosis cases reported in GeoSentinel from January 1997 through December 2016. We included 180 travelers with leptospirosis (mostly male; 74%; mostly tourists; 81%). The most frequent region of infection was Southeast Asia (52%); the most common source countries were Thailand (N = 52), Costa Rica (N = 13), Indonesia, and Laos (N = 11 each). Fifty-nine percent were hospitalized; one fatality was reported. We also distributed a supplemental survey to GeoSentinel sites to assess clinical and diagnostic practices. Of 56 GeoSentinel sites, three-quarters responded to the survey. Leptospirosis was reported to have been most frequently considered in febrile travelers with hepatic and renal abnormalities and a history of freshwater exposure. Serology was the most commonly used diagnostic method, although convalescent samples were reported to have been collected infrequently. Within GeoSentinel, leptospirosis was diagnosed mostly among international tourists and caused serious illness. Clinical suspicion and diagnostic workup among surveyed GeoSentinel clinicians were mainly triggered by a classical presentation and exposure history, possibly resulting in underdiagnosis. Suboptimal usage of available diagnostic methods may have resulted in additional missed, or misdiagnosed, cases.

Spotted fever group rickettsioses (SFGRs), such as African tick bite fever (ATBF), are among the most commonly diagnosed diseases for ill travelers returning from southern Africa. We summarized demographic, clinical, and diagnostic features of imported SFGR cases in U.S. travelers returning from Africa who had laboratory specimens submitted to the Centers for Disease Control and Prevention. Diagnosis of SFGR was performed by indirect immunofluorescence antibody assay, immunohistochemical staining, polymerase chain reaction (PCR), or culture. Cases were defined as probable SFGR, confirmed SFGR, or confirmed ATBF. Clinical and epidemiological categorical variables were described as counts and proportions; continuous variables were described using geometric mean titers, median, and range. One hundred and twenty-seven patients satisfied laboratory criteria for confirmed or probable SFGR. Fever was the most common symptom (N = 88; 69%), followed by ≥ 1 eschars (N = 70; 55%). Paired serums were submitted for 36 patients (28%); 12 patients (33%) had nonreactive initial serum sample but converted to a titer ≥ 64 with the convalescent sample. Twenty-seven patients (21%) had infection with Rickettsia africae based on PCR analysis of eschar swab (N = 8) or biopsy (N = 23). Fifteen patients had eschar biopsy or swab samples and serum sample(s) submitted together; 9 (60%) had PCR-positive eschar results and nonreactive acute serology. Health-care providers should consider SFGR when evaluating patients for a febrile illness with eschar and compatible foreign travel history. Polymerase chain reaction testing of eschar biopsies or swabs provides a confirmed diagnosis in early stages of disease; eschar swabs or biopsies are an underutilized diagnostic technique.

Delay in diagnosis and treatment worsens the disease and clinical outcomes, which further enhances transmission of tuberculosis (TB) in the community. Therefore, this study aims to assess treatment delay and its associated factors among pulmonary TB patients in Pakistan. A cross-sectional study was conducted among 269 pulmonary TB patients in the district. Binary and multivariate logistic regressions were used to explore the factors associated with delay in TB treatment. Results reveal that most patients were from low socioeconomic backgrounds. For example, 74.7% were living in kacha houses, 54.7% were from lowest the income group (< 250 US$/month), 60.2% married, 54.3% illiterate, 62.5% rural, 56.1% had no house ownership, and 56.5% had insufficient income for daily family expenditures. Significant delays were revealed by this study: 160 patients had experienced a delay of more than 4 weeks, whereas the median delay was 5 weeks. Results show that the most important reason for patient delay was low income and poverty (42.0%) followed by unaware of TB center (41.6), stigma (felt ashamed = 38.7%), and treatment from local traditional healers. Old age (adjusted odds ratio [AOR] = 6.6; 95% confidence interval [CI] = 1.63–26.95); and rural areas patients (AOR = 2.1; 95% CI = 1.15–3.71) were more likely to have experienced delay. However, the higher income and sufficient income category (AOR = 0.5; 95% CI = 0.31–0.95) were associated factors and less likely to experience delay in patient treatment. Integrative prevention interventions, such as those involving community leaders, health extension workers such as lady health workers, and specialized TB centers, would help to reduce delay and expand access to TB-care facilities.

Trachoma surveillance is typically performed via random sampling of endemic districts. This strategy minimizes bias and allows examination of preschool children, but is also expensive. Surveillance for some other neglected tropical diseases is carried out in schools, which is logistically easier. In the present study, the prevalence of trachomatous inflammation–follicular (TF) from a population-based sample of children from each of 70 communities in Ethiopia was compared with the corresponding school-based estimate, which was calculated for each community by performing examinations in all primary schools in the district. The overall prevalence of TF was 39.1% (95% confidence interval [CI]: 35.0–43.1%) among children aged 1–9 years in the community-based sample and 18.8% (95% CI: 15.9–21.7%) among children in grades 1–3 of the school-based sample. School-based estimates of TF explained 35% of the variation in the community-based prevalences (P < 0.001). When TF prevalence was used as a diagnostic test for detecting a community with > 5% prevalence of ocular chlamydia, the area under the receiver operating characteristic curve was 0.73 (95% CI: 0.60–0.85) for the school-based sample and 0.71 (0.58–0.83) for the community-based sample (P = 0.76). Thus, although school-based monitoring was necessarily biased relative to population-based monitoring of 1- to 9-year olds, the two methods provided a similar amount of information about the community burden of ocular chlamydia in this trachoma-hyperendemic setting. The generalizability of these findings to areas with less prevalent trachoma is unclear.

Staphylococcus aureus is a common cause of bloodstream infection and methicillin-resistant S. aureus (MRSA) is a growing threat worldwide. We evaluated the incidence rate of S. aureus bacteremia (SAB) and MRSA from population-based surveillance in all hospitals from two Thai provinces. Infections were classified as community-onset (CO) when blood cultures were obtained ≤ 2 days after hospital admission and as hospital-onset (HO) thereafter. The incidence rate of HO-SAB could only be calculated for 2009–2014 when hospitalization denominator data were available. Among 147,524 blood cultures, 919 SAB cases were identified. Community-onset S. aureus bacteremia incidence rate doubled from 4.4 (95% confidence interval [CI]: 3.3–5.8) in 2006 to 9.3 per 100,000 persons per year (95% CI: 7.6–11.2) in 2014. The highest CO-SAB incidence rate was among adults aged 50 years and older. Children less than 5 years old had the next highest incidence rate, with most cases occurring among neonates. During 2009–2014, there were 89 HO-SAB cases at a rate of 0.13 per 1,000 hospitalizations per year (95% CI: 0.10–0.16). Overall, MRSA prevalence among SAB cases was 10% (90/911) and constituted 7% (55/736) of CO-SAB and 20% (22/111) of HO-SAB without a clear temporal trend in incidence rate. In conclusion, CO-SAB incidence rate has increased, whereas MRSA incidence rate remained stable. The increasing CO-SAB incidence rate, especially the burden on older adults and neonates, underscores the importance of strong SAB surveillance to identify and respond to changes in bacteremia trends and antimicrobial resistance.

Chromobacterium violaceum is a rare, potentially serious pathogen. Most clinicians have no experience with its clinical appearance or treatment. We describe a case of a child presenting with necrotizing pneumonia caused by C. violaceum. We describe case complexities, including the need for a multidisciplinary approach to diagnosis and treatment.

Three cases of cholera occurred in South Korea during a period of three weeks in August 2016. All the cases were associated with the consumption of raw seafood in southern coastal area of South Korea. Epidemiologic investigations were performed to track the spread of cholera, including persons in contact with the cholera patients, seafood, and seawater from the fish tank and marine environments. A microbiological investigation demonstrated that cholera isolated from the three patients and a seawater sample at the Korea Strait showed identical serotype (O1 Ogawa), biotype (El tor), and toxin (ctx-positive). Pulsed-field gel electrophoresis analysis showed that the three clinical strains are identical (100%) and shared 97% identity with the seawater sample.

Diarrhea remains a leading cause of morbidity and mortality in patients worldwide. The objective of this study was to determine the relative inter-rater reliability and usability of standard and Mobile health (mHealth)-supported World Health Organization (WHO) algorithms for dehydration assessment in patients with acute diarrhea in a rural, low-income country hospital. Two nurses blinded to each other’s examinations assessed dehydration status on patients soon after hospital arrival using either the standard WHO algorithm printed on a laminated card or an mHealth-supported WHO algorithm downloaded onto a smartphone. The assignment of assessment tool was based on odd or even enrollment date. The inter-rater reliability for dehydration assessment between the two nurses was calculated using Cohen’s K statistic for each study group. A total of 496 patients (< 5 years N = 349, > 5 years N = 147) were enrolled in the study; 132 (27%) had some or severe dehydration, and 364 (73%) had no dehydration on arrival. Cohen’s K statistic demonstrated greater reliability for the mHealth-supported dehydration assessment (0.59) compared with the standard assessment (0.50) in the overall population (P < 0.0001), as well as in the pediatric (0.43 versus 0.37, P < 0.0001) and adult (0.79 versus 0.57, P < 0.0001) populations individually. This is the first study to show that mHealth can improve the reliability of nursing dehydration assessment in patients with acute diarrhea and the first to report on the reliability of the WHO algorithm in adult patients specifically. Future studies should focus on the impact of mHealth-supported dehydration assessment on patient-centered outcomes and examine its reliability in different settings worldwide.

Tick-borne encephalitis (TBE) is widely prevalent on the Eurasian continent, including Japan, but four cases of TBE have been reported in Japan. To inspect unconfirmed TBE cases in Japan, we conducted a retrospective seroepidemiological study of a total of 158 samples from 81 meningoencephalitis patients suspected as Lyme disease. Two serum samples from one patient showed neutralizing antibodies against TBE virus. The patient with severe and progressive encephalitis had a history of tick bite in Hokkaido in 2012. These results demonstrated that tick-borne encephalitis virus (TBEV) case was actually unconfirmed in Japan. Further seroepidemiological surveys are required to identify unconfirmed TBEV infections to consider the pros and cons of introducing specific countermeasures including vaccination in Japan.

Chronic stage chikungunya (CHIK), defined by persisting symptoms more than 3 months after initial diagnosis of acute infection, is frequent. However, its burden and impact have rarely been described prospectively in a general population during an ongoing epidemic in the Caribbean. From January 2014 to January 2015, a severe CHIK outbreak occurred in Martinique. Our objective was to describe epidemiological characteristics and outcomes of chronic stage CHIK in its local population. Participants, clinically diagnosed with probable CHIK infection, were included prospectively by general practitioners during the epidemic’s peak from April to October 2014. All identified cases benefited from a follow-up phone call 3 months or more after initial diagnosis during which they were interrogated about persisting clinical signs, past and ongoing treatment, and quality of life. Five hundred and nine subjects participated in the study. Mean age at initial diagnosis was 43.2 ± 23.6 years with a female–male ratio of 1.98. Two hundred participants (39.3%) had probable chronic stage CHIK: 98.5% still experienced pain at least 3 months after acute infection, with 84.3% of reported joint pains; 21.2% were woken up by the pain; 47.2% felt depressed/anxious; and 31.3% experienced memory/concentration disorders. Resumption of daily activity and work was complicated for 55.8% and 36.2% of cases. Persistent impact on morbidity, health outcomes, psychological, and economic aspects further underline the crucial role of community-based medicine and the necessity of an evidence-based multidisciplinary approach toward chronic stage CHIK identification, management, and follow-up in this particular world region.

A total of 1,090 residents of the city of Reynosa, Tamaulipas, on the Mexico–U.S. border presented at hospitals and clinics of the Secretariat of Health, Mexico, in 2015 with symptoms characteristic of dengue. Dengue virus (DENV) antigen was detected by enzyme-linked immunosorbent assay in acute sera from 134 (12.3%) patients. Sera from select patients (N = 34) were also tested for chikungunya virus (CHIKV) RNA by quantitative reverse transcription–polymerase chain reaction. Thirteen (38.2%) patients, including five DENV antigen-positive patients, were positive. Sera from three CHIKV RNA-positive patients were further assayed by virus isolation in cell culture and CHIKV was recovered on each occasion. The genome of one isolate and structural genes of the other two isolates were sequenced. In conclusion, we present evidence of CHIKV and DENV coinfections in patients who live near the Mexico–U.S. border and provide the first genome sequence of a CHIKV isolate from northern Mexico.

Dengue, a viral mosquito-borne disease currently affects more than 2.5 billion people living in endemic areas worldwide. In vector control, social mobilization and community behavioral changes are of crucial importance. Here, we identified the factors influencing community dengue preventive practices in a high-transmission urban area in Venezuela. Between September 2013 and February 2014, a cross-sectional study at the household level was carried out in Maracay city, Venezuela. A precoded questionnaire was used to obtain information on people’s knowledge, attitudes, and use of preventive practices in relation to dengue. Concomitantly, entomological data was collected from households. In 80% of the 105 included households, 1–5 preventive practices (e.g., repellents, insecticides) against mosquito bites were used. However, 57% of the examined houses had potential Aedes breeding sites indoors and/or outdoors, most of which positive for Aedes spp. larvae/pupae. Preventive practices were associated with a previous dengue infection (P = 0.030) and a better knowledge on dengue symptoms and transmission route (P = 0.020). In turn, knowledge was associated with feeling at risk (P < 0.001), a previous dengue infection (P = 0.010), and reported exposure to information sources of dengue (P = 0.011). Even though the knowledge level of the community over transmission ways was high, and most of the individuals took measures to avoid mosquito bites, potential mosquito breeding sites were present in almost two-thirds of the examined properties. Health promotion activities in Venezuela should aim at raising awareness at the community level on the importance of combining mosquito bite prevention with removal of breeding sites in and around the households.

Singapore has experienced periodic dengue epidemics despite maintaining a low Aedes house index. Each epidemic was associated with a switch in the predominant serotype. We investigated the temporal dynamics of dengue fever and dengue virus (DENV) and analyzed the epidemiological and entomological patterns of dengue in Singapore from 2004 to 2016. The case surveillance is based on a mandatory notification system that requires all medical practitioners to report clinically suspected and laboratory-confirmed cases. Circulating (DENV) serotypes are monitored through a virus surveillance program. Entomological surveillance involves inspections for larval breeding and monitoring of adults using gravitraps. Singapore experienced a similar epidemic pattern during 2004–2007 and 2013–2016. The pattern involved a 2-year DENV-1 epidemic occurring after a switch in the predominant serotype from DENV-2 to DENV-1, followed by a “lull” year. Thereafter, the predominant serotype switched back to DENV-2, tailed by a small-scale epidemic. Across the years, the highest incidence group was in the 25–44 years age group. The incidence rate of those aged ≥ 55 years was about half of that of the 15–24 years age group during DENV-1 predominant years. However, it was almost equal to the younger age group in DENV-2 predominant years. Types of Aedes aegypti breeding habitats remained similar. Dengue incidence was significantly higher in areas with high breeding percentage (BP) than areas with low BP (P < 0.05). In conclusion, the oscillation of DENV-1 and DENV-2, throughout the 13-year period, led to a cyclical epidemic pattern and older adults were more affected by DENV-2 than DENV-1.

Few studies have evaluated the effectiveness of Zika virus (ZIKV) public health educational campaigns. Following a ZIKV educational campaign in Roatán, Honduras (October 2016), a survey was administered (March–May 2017) to residents (N = 348) and health-care professionals ([HCPs]; N = 44) to evaluate ZIKV knowledge, attitudes, and preventive practices, with attention to sexual health. Knowledge scores were calculated and mapped using participants’ home locations. The knowledge scores between HCPs and residents were significantly different (mean 17 versus 11; P < 0.001). Only 6% of residents and 14% of HCPs knew that ZIKV was sexually transmissible. Few reported abstinence (2.6% residents; 9.4% HCPs) or condom use (1.6% residents; 12.5% HCPs) to prevent ZIKV infection. Of all subjects, 15.6% were pregnant or had a pregnant partner in the past year; 57.6% expressed concern over ZIKV. Mapping demonstrated spatial heterogeneity in knowledge. The findings suggest a need for improved public health messaging in ZIKV-affected areas.

St.Louis encephalitis virus (SLEV) is an emerging human pathogen flavivirus in Argentina. Recently, it has reemerged in the United States. We evaluated the role as amplifying host of six resident bird species and analyzed their capacity as host during the 2005 encephalitis outbreak of SLEV in Córdoba. Eared Dove, Picui Ground Dove, and House Sparrow were the three species with highest host competence index. At a city level, Eared Dove and Picui Ground Dove were the most important amplifying hosts during the 2005 SLEV human outbreak in Córdoba city. This finding highlighted important differences in the SLEV ecology between Argentina and the United States. Characterizing and evaluating the SLEV hosts contribute to our knowledge about its ecology and could help us to understand the causes that promote its emergence as a human pathogen in South America.

Anthropogenic land use change, including agriculture, can alter mosquito larval habitat quality, increase mosquito abundance, and increase incidence of vector-borne disease. Rice is a staple food crop for more than half of the world’s population, with ∼1% of global production occurring within the United States (US). Flooded rice fields provide enormous areas of larval habitat for mosquito species and may be hotspots for mosquito-borne pathogens, including West Nile virus (WNV). West Nile virus was introduced into the Americas in 1999 and causes yearly epidemics in the US with an average of approximately 1,400 neuroinvasive cases and 130 deaths per year. We examined correlations between rice cultivation and WNV disease incidence in rice-growing regions within the US. Incidence of WNV disease increased with the fraction of each county under rice cultivation in California but not in the southern US. We show that this is likely due to regional variation in the mosquitoes transmitting WNV. Culex tarsalis was an important vector of WNV in California, and its abundance increased with rice cultivation, whereas in rice-growing areas of the southern US, the dominant WNV vector was Culex quinquefasciatus, which rarely breeds in rice fields. These results illustrate how cultivation of particular crops can increase disease risk and how spatial variation in vector ecology can alter the relationship between land cover and disease.

Acute conjunctivitis follows a seasonal pattern. Although its clinical course is typically self-limited, conjunctivitis epidemics incur a substantial economic burden because of missed school and work days. This study investigated seasonal and temporal trends of childhood conjunctivitis in the entire country of Burkina Faso from 2013 to 2016, using routine monthly surveillance from 2,444 government health facilities. A total of 783,314 cases were reported over the 4-year period. Conjunctivitis followed a seasonal pattern throughout the country, with a peak in April. A nationwide conjunctivitis outbreak with a peak in September 2016 was noted (P < 0.001), with an excess number of cases first detected in June 2016. Nationwide passive surveillance was able to detect an epidemic 3 months before its peak, which may aide in allocation of resources for containment and mitigation of transmission in future outbreaks.

This study evaluated a newly developed paper analytical device (PAD) for screening amoxicillin samples in Blantyre urban townships. Covert shoppers attempted to buy amoxicillin from a geographically stratified selection of private pharmacies (N = 22 out of 26) and drug stores (N = 23 out of 103) in the township area. According to the PAD results, all 42 samples obtained by the shoppers contained amoxicillin and none contained suspicious filler materials. Next, the products were assayed using high-performance liquid chromatography. Consistent with the PAD results, all samples contained the correct amount of amoxicillin with no unexpected ingredients. However, one sample was purchased as amoxicillin and contained that ingredient, but was packaged in capsules that are normally used to package ampicillin. Almost every sample failed a simple packaging analysis. Nine in 10 samples were missing their original packaging and/or inserts (52.4% repackaged capsules and 35.7% repackaged blister packs). Only 33.3% of the packages had expiry dates, 16.7% had batch numbers, and 47.6% had the manufacturer’s name. Dispensing practices were likewise unsatisfactory. Ninety-five percentage of the sellers sold the amoxicillin without a prescription, even though this medicine is regulated as prescription-only in Malawi. Although the chemical analysis showed that amoxicillin quality was good, our market survey revealed poor adherence to prescription-only medicine dispensing of antibiotics, which threatens antimicrobial stewardship efforts. Furthermore, the wide prevalence of repackaging deprives medicines of important information needed during patient’s use, regulatory investigations, and pharmacovigilance reporting.