The American Journal of Tropical Medicine and Hygiene - Volume 88, Issue 3, March 2013

Clinical definitions of melioidosis and inhalation-acquired melioidosis (Burkholderia pseudomallei infection) are described together with the evidence used to develop these definitions. Such definitions support accurate public health reporting, preparedness planning for deliberate B. pseudomallei release, design of experimental models, and categorization of naturally acquired melioidosis.

Immunization remains the most cost effective method for the control of infectious diseases. Therefore, there is a global effort to deploy new vaccines for disease control and eradication. These new vaccines must be tested in the settings in which they will be used. This necessity has required the conduct of many vaccine trials in Africa, where several infectious diseases with significant public health impact are prevalent. However, these areas have peculiarities and are just beginning to gain expertise in the conduct of such trials. The vaccine developers and sponsors of these trials may also not be conversant with some issues unique to the trial site. The understanding gap from both partners can result in challenges if not addressed during the planning phase of the trial. This review seeks to highlight the issues surrounding the conduct of clinical trials in resource-constrained settings and suggests some ways of circumventing them.

Since the first case of strongyloidiasis reported in China in 1973, there have been 330 confirmed cases as of 2011. The present study conducted a meta-analysis on 106 cases for which detailed information on clinical symptoms, diagnosis, and outcome was available. Most (63%) cases were from the past decade. Immunocompromised patients and those given cortical hormones accounted for 68% of the cases, and case-fatality rate was 38%. General clinical symptoms included abdominal pain (53%), diarrhea (46%), fever (40%), and vomiting (39%). The parasite positivity rate in feces, sputum, and urine by microscopic diagnosis was 75%, 24%, and 8%, respectively, and gastrointestinal endoscopy or other biopsy detection rates were 17%. A lack of specific clinical manifestations makes early diagnosis and correct treatment difficult. Strongyloidiasis is an emerging disease in China, and public and clinical awareness needs to be raised to improve prevention and control.

We evaluated a commercial point-of-care circulating cathodic antigen (POC-CCA) test for assessing Schistosoma mansoni infection prevalence in areas at risk. Overall, 4,405 school-age children in Cameroon, Côte d'Ivoire, Ethiopia, Kenya, and Uganda provided urine for POC-CCA testing and stool for Kato-Katz assays. By latent class analysis, one POC-CCA test was more sensitive (86% versus 62%) but less specific (72% versus ∼100%) than multiple Kato-Katz smears from one stool. However, only 1% of POC-CCA tests in a non-endemic area were false positives, suggesting the latent class analysis underestimated the POC-CCA specificity. Multivariable modeling estimated POC-CCA as significantly more sensitive than Kato-Katz at low infection intensities (< 100 eggs/gram stool). By linear regression, 72% prevalence among 9–12 year olds by POC-CCA corresponded to 50% prevalence by Kato-Katz, whereas 46% POC-CCA prevalence corresponded to 10% Kato-Katz prevalence. We conclude that one urine POC-CCA test can replace Kato-Katz testing for community-level S. mansoni prevalence mapping.

We measured prevalence of Schistosoma haematobium, Wuchereria bancrofti, Plasmodium falciparum, hookworm, and other geohelminths among school-aged children in four endemic villages in Kwale County, Kenya and explored the relationship between multiparasite burden, undernutrition, and anemia. In 2009–2010 surveys, cross-sectional data were obtained for 2,030 children 5–18 years old. Infections were most prevalent for S. haematobium (25–62%), hookworm (11–28%), and falciparum malaria (8–24%). Over one-half of children were anemic, with high rates of acute and chronic malnutrition. Associations with infection status showed significant age and sex differences. For boys, young age, low socioeconomic standing (SES), S. haematobium, and/or malaria infections were associated with greater odds of anemia, wasting, and/or stunting; for girls, heavy S. haematobium infection and age were the significant cofactors for anemia, whereas low SES and older age were linked to stunting. The broad overlap of infection-related causes for anemia and malnutrition and the high frequency of polyparasitic infections suggest that there will be significant advantages to integrated parasite control in this area.

Preventive chemotherapy with praziquantel is recommended in adults by the World Health Organization when prevalence of schistosomiasis in school-aged children (SAC) is ≥ 50%. This study ascertained the value of this threshold in predicting prevalence and intensity of Schistosoma hematobium (SH) infection in adults in central Nigeria. We evaluated urogenital schistosomiasis prevalence in 1,164 adults: 659 adults in 12 communities where mean hematuria among SAC in 2008 was 26.6% and 505 adults in 7 communities where the mean hematuria among SAC in 2008 was 70.4%. No statistically significant differences were found between the two groups of adults in prevalence of hematuria, prevalence of SH eggs, or intensity of infections. We conclude that, in this setting, the SAC threshold is not useful for treatment decisions in adults. Given the increased risk of subtle morbidity or urogenital schistosomiasis as a risk factor for human immunodeficiency virus (HIV), more liberal treatment of adults with praziquantel is warranted.

Higher levels of viremia and circulating nonstructural protein 1 (NS1) have been associated with dengue disease severity. In this study, viremia and circulating NS1 levels were determined in 225 serum samples collected from patients in Mexico infected with dengue virus serotypes 1 and 2 (DENV-1 and DENV-2). Patients with dengue hemorrhagic fever (DHF) who were infected with DENV-1 showed higher levels of circulating NS1 than patients with dengue fever (DF) (P = 0.0175). Moreover, NS1 levels were higher in patients with primary infections with DENV-1 than in patient infected with DENV-2 (P < 0.0001) and in patients with primary infections with DENV-2 than in patients with secondary infections with DENV-2 (P = 0.0051). Unexpectedly, viremia levels were higher in patients with DF than in those with DHF infected with either DENV-1 or DENV-2 (P = 0.0019 and P = 0.001, respectively) and in patients with primary infections than those with secondary DENV-2 infections (P < 0.0001). Results indicate that levels of circulating NS1 vary according to the infecting serotype, immunologic status (primary or secondary infection), and dengue disease severity.

The long-term persistence of Modoc virus (MODV) infection was investigated in a hamster model. Golden hamsters (Mesocricetus auratus) were infected by subcutaneous inoculation with MODV, in which fatal encephalitis developed in 12.5% (2 of 16). Surviving hamsters shed infectious MODV in their urine during the first five months after infection, and infectious MODV was recovered by co-cultivation of kidney tissue up to eight months after infection. There were no histopathologic changes observed in the kidneys despite detection of viral antigen for 250 days after infection. Mild inflammation and neuronal degeneration in the central nervous system were the primary lesions observed during early infection. These findings confirm previous reports of persistent flavivirus infection in animals and suggest a mechanism for the maintenance of MODV in nature.

Pneumonia was the most common cause of death during the 2009 pandemic H1N1 influenza virus infection. Clinical risk factors for pneumonia caused by this virus are limited. We enrolled consecutive patients treated at the H1N1 Clinic in Thungsong Hospital in Nakhon Si Thammarat, Thailand, during June–December 2009 who had positive polymerase chain reaction results for H1N1 virus. Clinical features for patients given a diagnosis with and without pneumonia were studied. There were 441 patients with positive polymerase chain reaction results for H1N1 virus. Of these patients, 51 (11.56%) had pneumonia. Three independent clinical factors for H1N1 pneumonia were myalgia, dyspnea, and an absolute neutrophil count > 7,700 cells/μL. Adjusted odds ratios (95% confidence intervals) for these three variables were 0.413 (0.173–0.988), 2.625 (1.230–5.604), and 4.475 (1.882–10.644), respectively. Clinical features may be a useful tool for predicting risk for pneumonia caused by H1N1 virus.

Wider availability of the live, attenuated SA 14-14-2 Japanese encephalitis (JE) vaccine has facilitated introduction or expansion of immunization programs in many countries. However, information on their impact is limited. In 2006, Nepal launched a JE immunization program, and by 2009, mass campaigns had been implemented in 23 districts. To describe the impact, we analyzed surveillance data from 2004 to 2009 on laboratory-confirmed JE and clinical acute encephalitis syndrome (AES) cases. The post-campaign JE incidence rate of 1.3 per 100,000 population was 72% lower than expected if no campaigns had occurred, and an estimated 891 JE cases were prevented. In addition, AES incidence was 58% lower, with an estimated 2,787 AES cases prevented, suggesting that three times as many disease cases may have been prevented than indicated by the laboratory-confirmed JE cases alone. These results provide useful information on preventable JE disease burden and the potential value of JE immunization programs.

Crimean-Congo hemorrhagic fever is a tick-borne viral zoonosis with the potential of human-to-human transmission with case fatality rates from 3% to 50%. The incubation period depends on host, route of infection, and viral dose. Herein, we report a nosocomial spread of the disease in a hospital at Mashhad, northeastern Iran, with a very short incubation period for one of the secondary cases. The patient was a medical student who had a negligible contact with a Crimean-Congo hemorrhagic fever patient during his admission to the hospital. The time interval between the contact and the onset of symptoms was merely 20 hours. Unfortunately, he died within 1 week of exposure.

In 2009, an increased proportion of suspected dengue cases reported to the surveillance system in Puerto Rico were laboratory negative. As a result, enhanced acute febrile illness (AFI) surveillance was initiated in a tertiary care hospital. Patients with fever of unknown origin for 2–7 days duration were tested for Leptospira, enteroviruses, influenza, and dengue virus. Among the 284 enrolled patients, 31 dengue, 136 influenza, and 3 enterovirus cases were confirmed. Nearly half (48%) of the confirmed dengue cases met clinical criteria for influenza. Dengue patients were more likely than influenza patients to have hemorrhage (81% versus 26%), rash (39% versus 9%), and a positive tourniquet test (52% versus 18%). Mean platelet and white blood cell count were lower among dengue patients. Clinical diagnosis can be particularly difficult when outbreaks of other AFI occur during dengue season. A complete blood count and tourniquet test may be useful to differentiate dengue from other AFIs.

A review of the laboratory-confirmed cases of Murray Valley encephalitis (MVE) from Western Australia between 2009 and 2011 was conducted to describe the clinical, laboratory, and radiological features of the disease. The nine encephalitis patients presented with altered mental state and seizures, tremor, weakness, or paralysis. All patients developed a raised C-reactive protein, whereas most developed acute liver injury, neutrophilia, and thrombocytosis. All patients with encephalitis developed cerebral peduncle involvement on early magnetic resonance imaging (MRI). The absence of thalamic MRI hyperintensity during the acute illness, with or without leptomeningeal enhancement, predicted a better neurological outcome, whereas those patients with widespread abnormalities involving the thalamus, midbrain, and cerebral cortex or the cerebellum had devastating neurological outcomes. MRI scans repeated months after acute illness showed destruction of the thalamus and basal ganglia, cortex, or cerebellum. These findings may help clinicians predict the neurological outcome when evaluating patients with MVE.

In Australia, dengue is not endemic, although the vector mosquito Aedes aegypti is established in far north Queensland (FNQ). Aedes albopictus has recently invaded the Torres Strait region, but is not established on mainland Australia. To maintain dengue-free, public health departments in FNQ closely monitor introduced dengue infections and confine outbreaks through rigorous vector control responses. To safeguard mainland Australia from Ae. albopictus establishment, pre-emptive strategies are required to reduce its breeding in difficult to access habitats. We compare the residual efficacy of VectoBac WDG, Bacillus thuringiensis var. israelensis (Bti) formulation, as a residual treatment when misted across a typical FNQ bushland using a backpack mister (Stihl SR 420 Mist Blower) at two dose rates up to 16 m. Semi-field condition results, over 16 weeks, indicate that Bti provided high mortality rates (> 80%) sustained for 11 weeks. Mist application penetrated 16 m of dense bushland without efficacy decline over distance.

Temperature is one of the most important environmental factors affecting biological processes of mosquitoes, including their interactions with viruses. In these studies, we show independent effects of rearing temperature on the immature aquatic stages and holding temperature on the adult terrestrial stage in terms of alterations in adult survival and progression of dengue-1 virus infection in the Asian tiger mosquito Aedes (Stegomyia) albopictus. Our studies show that adult survival was determined by adult-holding temperature, regardless of rearing conditions of the immature stages. In contrast, spread of virus throughout the body of the mosquito, a pre-requisite for transmission, was reduced when the immature stages were reared in cool conditions. These results show that immature-rearing temperature selectively modified mosquito traits that influence competency for viruses, and they further our understanding of the nature of temperature effects on interactions between mosquitoes and virus pathogens and risk of disease transmission.

Despite the availability of many methods for rapid and early diagnosis of dengue, there is still a need to develop new approaches that not only combine low cost, specificity, and sensitivity, but also are capable of accurately detecting secondary infection in the early stages of the disease. We report the potential of the high mobility group box 1 protein as an auxiliary biomarker for early dengue diagnosis. We tested a 205-sample serum panel that included negative and positive samples from primary and secondary dengue cases, as well as samples from patients with dengue-like symptoms. We observed that high mobility group box 1 protein was generally detected only in dengue-positive samples for persons with primary and secondary infections. These results highlight the possibility of using this endogenous molecule as an auxiliary biomarker to aid in dengue detection and improve current methods for early diagnosis of dengue.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease in China. Polymerase chain reaction and enzyme-linked immunosorbent assay were used to detect SFTS virus (SFTSV) and Anaplasma phagocytophilum in previous clinically diagnosed human anaplasmosis patients and SFTS patients. A serosurvey for SFTSV infection was also conducted on healthy persons and animals in Yiyuan County in Shandong Province of China. Among 21 patients SFTSV was detected in 17 (81%) however A. phagocytophilum was not detected in any of the patients. The seroprevalence rate of IgG antibody to SFTSV antigens was 1.3% (1 of 78) in healthy persons, 95% (19 of 20) in goats, 50% (1 of 2) in dogs, 0% in cattle (0 of 21), and rats (Rattus norvegicus) (0 of 35). The conclusion of this study was that co-infection of SFTSV and A. phagocytophilum are rare in SFTS patients and goats might play an important role in transmission of SFTSV.

We conducted serological surveys for Coxiella burnetii in archived sera from patients that visited a rural clinic in western Kenya from 2007 to 2008 and in cattle, sheep, and goats from the same area in 2009. We also conducted serological and polymerase chain reaction-based surveillance for the pathogen in 2009–2010, in human patients with acute lower respiratory illness, in ruminants following parturition, and in ticks collected from ruminants and domestic dogs. Antibodies against C. burnetii were detected in 30.9% (N = 246) of archived patient sera and in 28.3% (N = 463) of cattle, 32.0% (N = 378) of goats, and 18.2% (N = 159) of sheep surveyed. Four of 135 (3%) patients with acute lower respiratory illness showed seroconversion to C. burnetii. The pathogen was detected by polymerase chain reaction in specimens collected from three of six small ruminants that gave birth within the preceding 24 hours, and in five of 10 pools (50%) of Haemaphysalis leachi ticks collected from domestic dogs.