The American Journal of Tropical Medicine and Hygiene - Current Issue

Early names for leptospirosis often indicate occupational or environmental exposure. Leptospirosis is hard to identify in the tropical setting because of co-circulating diseases. This is not the case in the temperate setting, such as Europe, where the few historical differential diagnoses were malaria, typhoid, and viral hepatitis. Leptospirosis presumably caused community epidemics in Europe before 1900 and military epidemiologists carefully documented outbreaks in “constrained settings.” Achille Kelsch (1841–1911) synthesized available military data and epidemiological perspectives to define “epidemic jaundice” as a nosological continuum, caused by an infectious agent found in muds and water. He viewed Weil’s disease as being only one form of that now well-identified disease continuum. The causative pathogen and epidemiological determinants were identified years later. The role of soils and muds as intermediate reservoirs, as suggested by Kelsch, deserves further investigation.

Enteric fever is a systemic bacterial infection in humans that is endemic in Cambodia and for which antibiotic resistance is increasingly reported. To guide public health programs, this qualitative study sought to explore community perceptions on transmission and treatment. Participant observation was carried out in hospital settings, pharmacies, and at a community level in Phnom Penh. In-depth interviews 39 and one focus group discussion were carried out with blood culture–confirmed enteric fever patients and purposively selected key informants. Informants were theoretically sampled based on initial themes identified using abductive analysis. Nvivo 11 was used for thematic coding. An urgent need to address health literacy concerning the transmission of enteric fever was identified, as lay informants did not link the disease and its symptoms to bacterial contamination of foods and drinks but rather to foods considered “bad” following humoral illness interpretations. As a result, lay informants considered recurrence of enteric fever preventable with appropriate dietary restrictions and Khmer traditional medicines. This study also reveals pluralistic health-care–seeking behavior. For initial and mild symptoms, patients preferred home treatment or traditional healing practices; limited household finances delayed treatment seeking. When symptoms persisted, patients first visited drug outlets or private practitioners, where they received a mix of nonessential medicines and one or more antibiotics often without prescription or confirmation of diagnosis. Inappropriate use of antibiotics was common and was related to diagnostic uncertainty and limited finances, factors which should be addressed during future efforts to improve the uptake of appropriate diagnostics and treatment of enteric fever.

Melioidosis is a major neglected tropical disease with high mortality, caused by the Gram-negative bacterium Burkholderia pseudomallei (Bp). Microbiological culture remains the gold standard for diagnosis, but a simpler and more readily available test such as an antibody assay is highly desirable. In this study, we conducted a serological survey of blood donors (n = 1,060) and adult melioidosis patients (n = 200) in northeast Thailand to measure the antibody response to Bp using the indirect hemagglutination assay (IHA). We found that 38% of healthy adults (aged 17–59 years) have seropositivity (IHA titer ≥ 1:80). The seropositivity in healthy blood donors was associated with having a declared occupation of rice farmer and with residence in a nonurban area, but not with gender or age. In the melioidosis cohort, the seropositivity rate was higher in adult patients aged between 18 and 45 years (90%, 37/41) compared with those aged ≥ 45 years (68%, 108/159, P = 0.004). The seropositivity rate was significantly higher in people with diabetes (P = 0.008). Seropositivity was associated with decreased mortality on univariable analysis (P = 0.005), but not on multivariable analysis when adjusted for age, diabetes status, preexisting renal disease, and neutrophil count. This study confirms the presence of high background antibodies in an endemic region and demonstrates the limitations of using IHA during acute melioidosis in this population.

Scrub typhus and Japanese spotted fever—both rickettsial diseases—are endemic and notifiable in Japan and may cause a fatal outcome without prompt treatment. Here we present the first case of a concurrent sympatric infection of both diseases with grade II evidence. A 67-year-old woman, after a single event of potential exposure to the pathogens, presented with a 12-day history of fever, pharyngeal pain, papulo-erythematous rash, and pronounced fatigue. Her erythematous rash was distributed on her trunk and extremities, palms, and soles and eventually progressed to purpura. Fever persisted until doxycycline was administered on day 12. A significant > 4-fold increase in immunoglobulin G and immunoglobulin M titers against multiple serotypes of Orientia tsutsugamushi and Rickettsia japonica were revealed by indirect immunoperoxidase assays. These clinical and serological data, even in the absence of molecular or isolation evidence, provided grade II evidence that this was a concurrent infection of sympatric scrub typhus and Japanese spotted fever.

Tuberculosis (TB) prevalence among incarcerated populations is as much as 1,000 times higher than in the general population. This study evaluates whether correctional facilities serve as a reservoir through which TB is transmitted to surrounding communities. Tuberculosis test data were extracted from the South African National Health Laboratory Service database for patients tested for TB between 2005 and 2011. We conducted graphical analysis to assess the relationship of TB rates between incarcerated and non-incarcerated populations over time. We performed generalized linear modeling with a log link function to assess TB risk in communities surrounding correctional facilities, net of confounders. We assessed linkages between incarcerated and non-incarcerated populations over time using Granger causality analysis. Tuberculosis prevalence among incarcerated populations was four times higher than in the general population. Tuberculosis incidence rates in incarcerated and non-incarcerated populations followed similar trends over time. The presence of a correctional facility in a municipality was associated with 34.9% more detected TB cases (confidence interval: 11.6–63.2; P < 0.01), controlling for potential confounders. Detected TB in incarcerated populations did not have predictive power in explaining detected TB rates in the non-incarcerated population after controlling for serial correlation in the time series data. Despite high TB prevalence, trends in correctional facilities do not appear to be driving temporal trends in the general population. However, correctional facilities still act as a TB reservoir that raises the overall TB risk in the vicinity. Intensified TB control policies for correctional facilities, formerly incarcerated individuals, and surrounding communities will reduce TB prevalence overall.

Vietnam has a high burden of tuberculosis (TB) and multidrug-resistant (MDR) TB, but drug resistance patterns and TB transmission dynamics among TB/human immunodeficiency virus (HIV) coinfected patients are not well described. We characterized 200 Mycobacterium tuberculosis isolates from TB/HIV coinfected patients diagnosed at the main TB referral hospital in Ho Chi Minh City, Vietnam. Phenotypic drug susceptibility testing (DST) for first-line drugs, spoligotyping, and 24-locus mycobacterial interspersed repetitive unit (MIRU-24) analysis was performed on all isolates. The 24-locus mycobacterial interspersed repetitive unit clusters and MDR isolates were subjected to whole genome sequencing (WGS). Most of the TB/HIV coinfected patients were young (162/174; 93.1% aged < 45 years) males (173; 86.5% male). Beijing (98; 49.0%) and Indo-Oceanic (70; 35.0%) lineage strains were most common. Phenotypic drug resistance was detected in 84 (42.0%) isolates, of which 17 (8.5%) were MDR; three additional MDR strains were identified on WGS. Strain clustering was reduced from 84.0% with spoligotyping to 20.0% with MIRU-24 typing and to 13.5% with WGS. Whole genome sequencing identified five additional clusters, or members of clusters, not recognized by MIRU-24. In total, 13 small (two to three member) WGS clusters were identified, with less clustering among drug susceptible (2/27; 7.4%) than among drug-resistant strains (25/27; 92.6%). On phylogenetic analysis, strains from TB/HIV coinfected patients were interspersed among strains from the general community; no major clusters indicating transmission among people living with HIV were detected. Tuberculosis/HIV coinfection in Vietnam was associated with high rates of drug resistance and limited genomic evidence of ongoing M. tuberculosis transmission among HIV-infected patients.

Human immunodeficiency virus/tuberculosis (HIV/TB) coinfection is particularly prevalent in South Africa, where TB has been the leading cause of death for more than a decade. The 2004–2008 national rollout of antiretroviral therapy (ART) provides a unique opportunity to examine the population-level impact of ART on the TB epidemic. We performed longitudinal regression analysis to follow the evolution of TB outcomes before and after the introduction of ART using a large data set from the National Health Laboratory Service. This is the first study to produce estimates of the impact of the ART rollout by exploiting staggered timing and geographic variation in the rollout. After ART became available in a health facility, 3.7% (P < 0.0001) more patients were tested for TB and 3.2% (P < 0.0001) more received repeat testing; however, there was a steep rise in testing before the introduction of ART. Although the number of TB-positive patients increased by 4.3% (P = 0.0002) in the first year post-ART, the TB rate among tested patients fell by 2 percentage points (8%, P = 0.001) after 2 years. Sputum smear testing declined relative to more technologically advanced diagnostics post-ART. Antiretroviral therapy availability increased the attention to TB screening and drew new patients into the health-care system. Small increases in the numbers of repeat patients are indicative of retention in care. The decline in TB rates post-ART suggests that the reduction in TB risk due to improved immune functioning and health-care contact likely outweighed the increased TB risk because of the longer lifespan of ART initiators.

Recent outbreaks of Chikungunya virus (CHIKV) infection confirm the vulnerability of neonates after vertical transmission. In 2014, CHIKV was reported for the first time in the Americas, including the island of Curaçao. We describe the outcomes of symptomatic neonates with vertically transmitted CHIKV infection during the CHIKV epidemic, who were admitted in the Saint Elisabeth Hospital, Willemstad, Curaçao. There were three symptomatic neonates with serologically confirmed infection. Two neonates developed neurological complications, including convulsions and intracerebral bleeding. One newborn, in whom maternal infection occurred 7 weeks before delivery, had a fatal outcome after birth. Maternal-fetal transmission of CHIKV may cause severe neonatal complications. There is a need to share experiences and to implement protocols toward the management of perinatal CHIKV infection.

We report here one case of Zika virus (ZIKV) infection associated with auto-immunity directed against the central nervous system in a Brazilian woman who developed acute transverse myelitis 9 days after recovery from an acute episode of fever with generalized erythema. Imaging of the spinal cord showed an elongated area on the T1–T10 level with gadolinium uptake. The diagnostic of the ZIKV infection was confirmed by cerebrospinal fluid and serum analysis. This patient had serum positivity for autoantibodies against myelin oligodendrocyte glycoprotein (MOG), a specific antibody against the myelin sheath. We propose that a direct central nervous system infection by ZIKV could lead to a specific auto-immunity against MOG protein.

Dengue is the most important arbovirosis in the world. In this study, we assessed the knowledge, attitudes, and practices (KAP) regarding dengue in parents from two small Colombian municipalities in the Cundinamarca Province. Parents and their healthy children from 4 to 14 years of age were included in some public elementary schools. After a medical examination, blood samples were taken for diagnosis of dengue using enzyme-linked immunosorbent assays (capture immunoglobulin M and capture immunoglobulin G [IgG], indirect IgG and detection non-structural viral protein 1) and detection of viral RNA by reverse transcription polymerase chain reaction. In addition, a KAP survey was applied to the children’s parents or tutors. The indirect IgG test determined that of the 347 examined children, 87.9% had a previous infection with the dengue virus (DENV), 12.7% of them were positive for viral RNA (asymptomatic infection), and 32.0% presented reinfections. Risk factors evaluation showed that children aged 8 years and older living in the municipalities for more than 7 years were more likely to be infected or reinfected by DENV. In the same way, poor nutrition, lack of water supply, sewer service, or waste disposal services could raise the likelihood of dengue infections. The surveys indicated that parents have unhealthy practices and a low knowledge about the transmission of the disease, which could result in an increase of mosquito breeding sites, allowing sustained dengue transmission.

Vaccine immunogenicity and clinical efficacy are often assessed by the measure of serum-neutralizing antibodies. The present gold standard for detecting neutralizing antibodies against many viruses, including dengue, is the plaque/focus reduction neutralization test (P/FRNT). The FRNT is a cell-based assay that inherits high variability, resulting in poor precision and has lengthy turnaround times. The virus reduction neutralization test (VRNT) is a high-throughput alternative to the standard low-throughput and laborious FRNT. The VRNT is similar to FRNT using unaltered wild-type virus and immunostaining, yet uses imaging cytometry to count virus-infected cells 1 day post-infection, reducing assay time and increasing overall throughput 15-fold. In addition, the VRNT has lowered variability relative to FRNT, which may be explained in part by the observation that foci overlap alters foci count and titer over time, in the FRNT. The ability to count one infected cell, rather than waiting for overlapping foci to form, ensures accuracy and contributes to the precision (7–25% coefficient of variation) and sensitivity of the VRNT. Results from 81 clinical samples tested in the VRNT and FRNT show a clear positive relationship. During sample testing, a 96-well plate edge effect was noted and the elimination of this edge effect was achieved by a simple plate seeding technique. The VRNT is an improvement to the current neutralization assays for its shortened assay time, increased precision and throughput, and an alternative to the P/FRNT.

Dengue virus (DENV) affects more than 100 countries worldwide. Dengue virus infection has been increasing in the southern Peruvian Amazon city of Puerto Maldonado since 2000. We designed this study to describe the prevalence of past DENV infection and to evaluate risk factors. In 2012, we conducted a cross-sectional serosurvey and administered a knowledge, attitudes, and practices (KAP) questionnaire to members of randomly selected households. Sera were screened for antibodies to DENV by enzyme-linked immunosorbent assay and confirmed by plaque reduction neutralization test. We created indices for KAP (KAPi). We used SaTScan (Martin Kulldorff with Information Management Services Inc., Boston, MA) to detect clustering and created a multivariate model introducing the distance of households to potential vector and infection sources. A total of 505 participants from 307 households provided a blood sample and completed a questionnaire. Fifty-four percent of participants (95% confidence interval [CI]: 49.6; 58.5) had neutralizing antibodies to DENV. Higher values of KAPi were positively associated with having DENV antibodies in the multivariate analysis (odds ratio [ORII]: 1.6, 95% CI: 0.6, 2.4; ORIII: 2.7, 95% CI: 1.3, 5.5; and ORIV: 2.4, 95% CI: 1.2, 5.0). Older groups had lower chances of having been exposed to DENV than younger people (OR20–30: 0.5, 95% CI: 0.2, 0.8; OR31–45: 0.5, 95% CI: 0.3, 0.9; and OR>45: 0.6, 95% CI: 0.3, 1.3). Multivariate data analysis from the 270 households with location information showed male gender to have lower risk of past DENV infection (OR: 0.6, 95% CI: 0.4, 0.9). We conclude that risk of DENV infection in Puerto Maldonado is related to gender, age of the population, and location.

Dengue virus (DENV) infection of humans is presently the most important arthropod-borne viral global threat, for which no suitable or reliable animal model exists. Reports addressing the effect of DENV on vascular components other than endothelial cells are lacking. Dengue virus infection of vascular smooth muscle cells, which play a physiological compensatory response to hypotension in arteries and arterioles, has not been characterized, thus precluding our understanding of the role of these vascular components in dengue pathogenesis. Therefore, we studied the permissiveness of primary human umbilical artery smooth muscle cells (HUASMC) to DENV 1–4 infection and compared with the infection in the previously reported primary human umbilical vein endothelial cells (HUVEC) and the classically used, non-transformed, and highly permissive Lilly Laboratories Cell-Monkey Kidney 2 cells. Our results show that HUASMC are susceptible and productive to infection with the four DENV serotypes, although to a lesser extent when compared with the other cell lines. This is the first report of DENV permissiveness in human smooth muscle cells, which might represent an unexplored pathophysiological contributor to the vascular collapse observed in severe human dengue infection.

As dengue causes about 4,000 symptomatic nonfatal episodes for every dengue death globally, quantitative disability assessments are critical to assess the burden of dengue and the cost-effectiveness of dengue control interventions. This systematic analysis of disability or quality of life lost from a symptomatic nonfatal dengue episode combined a systematic literature review, statistical modeling, and probabilistic sensitivity analyses. We conceptualized a dengue episode as having two phases: acute and persistent symptoms. Our estimates for the acute phase, consisting of onset and recovery periods and defined as the first 20 days (0.054 year), were based on literature review. We searched PubMed, POPLINE, EconLit, Google Scholar, scientific conferences, and other sources, for “dengue” plus “quality of life” or related terms. From 4,322 initial entries, six met our criteria (original studies with empirical data). The median disability-adjusted life year (DALY) burden for the acute phase was 0.011 (95% certainty interval [CI]: 0.006–0.015) for ambulatory episodes, 0.015 (CI: 0.010–0.020) for hospitalized episodes, and 0.012 (CI: 0.006–0.019) overall. Using literature reviews about persistent dengue, we estimated that 34% of episodes experienced persistent symptoms with a median duration of symptoms of 0.087 (CI: 0.040–0.359) year, which resulted in median DALYs of 0.019 (CI: 0.008–0.082). Thus, the overall median DALY burden was 0.031 (CI: 0.017–0.092) for ambulatory episodes, 0.035 (CI: 0.024–0.096) for hospitalized episodes, and 0.032 (CI: 0.018–0.093) overall. Our dengue-specific burden of a dengue episode was 2.1 times the 2013 Global Burden of Disease estimate. These literature-based estimates provide an empirical summary for policy and cost-effectiveness analyses.

We describe the case of a patient with severe fever with thrombocytopenia syndrome (SFTS) complicated by SFTS-associated encephalopathy who was successfully treated with 4-day plasma exchange followed by two-time convalescent plasma therapy. During plasma exchange, the plasma cytokines interferon-α and inducible protein-10 gradually decreased without change of plasma viral load. However, plasma viral load gradually decreased after convalescent plasma therapy. This case provides important insights for understanding the mechanisms of experimental therapy in severely affected SFTS patients.

Global evidence suggests that hepatitis B viral (HBV) infection is endemic in Africa and perinatal transmission remains one of the most important modes of HBV transmission in this area. This cross-sectional survey examined the seroprevalence and knowledge of hepatitis B among pregnant women attending antenatal clinic (ANC) in a mission hospital in Ghana. Systematic sampling technique was used to recruit 196 pregnant women. The level of statistical significance was set at 0.05 alpha level. The hepatitis B prevalence estimate (hepatitis B surface antigen) was 10.2% (N = 20) and all of the participants were aware of HBV infection. Majority cited media (radio) as their main source of information. Approximately 86% of the participants (N = 168) associated HBV infection with a curse and 88.8% (N = 174) indicated witches and wizards as possible causes of the infection. Those with higher level of school education had high hepatitis B knowledge score (P < 0.01). Implementation of a health education program on the route of hepatitis B transmission is required in the study setting. Also, inclusion of hepatitis B education as part of ANC activities will enable HBV-positive pregnant women to appreciate the need for hepatitis B vaccination of their newborns at birth.