The American Journal of Tropical Medicine and Hygiene - Volume 89, Issue 2, 2013

One hundred and eighty febrile patients were analyzed in a prospective evaluation of Orientia tsutsugamushi and Rickettsia spp. real-time polymerase chain reaction (PCR) assays for early diagnosis of rickettsial infections. By paired serology, 3.9% (7 of 180) and 6.1% (11 of 180) of patients were confirmed to have acute scrub or murine typhus, respectively. The PCR assays for the detection of O. tsutsugamushi and Rickettsia spp. had high specificity (99.4% [95% confidence interval (CI): 96.8–100] and 100% [95% CI: 97.8–100], respectively). The PCR results were also compared with immunoglobulin M (IgM) immunofluorescence assay (IFA) on acute sera. For O. tsutsugamushi, PCR sensitivity was twice that of acute specimen IgM IFA (28.6% versus 14.3%; McNemar's P = 0.3). For Rickettsia spp., PCR was four times as sensitive as acute specimen IgM IFA (36.4% versus 9.1%; P = 0.08), although this was not statistically significant. Whole blood and buffy coat, but not serum, were acceptable specimens for these PCRs. Further evaluation of these assays in a larger prospective study is warranted.

The aim of this translational study was to show the use of molecular surveillance for polymorphisms and copy number as a monitoring tool to track the emergence and dynamics of Plasmodium falciparum drug resistance. A molecular baseline for Suriname was established in 2005, with P. falciparum chloroquine resistance transporter (pfcrt) and P. falciparum multidrug resistance (pfmdr1) markers and copy number in 40 samples. The baseline results revealed the existence of a uniformly distributed mutated genotype corresponding with the fully mefloquine-sensitive 7G8-like genotype (Y184F, S1034C, N1042D, and D1246Y) and a fixed pfmdr1 N86 haplotype. All samples harbored the pivotal pfcrtK76T mutation, showing that chloroquine reintroduction should not yet be contemplated in Suriname. After 5 years, 40 samples were assessed to trace temporal changes in the status of pfmdr1 polymorphisms and copy number and showed minor genetic alterations in the pfmdr1 gene and no significant changes in copy number, thus providing scientific support for prolongation of the current drug policy in Suriname.

The Military Health System (MHS), with 9.7 million beneficiaries, represents an enormous pool of potential travelers requiring malaria prevention measures. A systematic search of the MHS electronic pharmacy record was performed for prescriptions of atovaquone-proguanil (AP), chloroquine (CQ), doxycycline (DC), mefloquine (MQ), primaquine (PQ) to adult patients from 2007 through 2011. Over 1,000,000 were identified, including 161,341 primary prophylaxis prescriptions originating from civilian facilities. Military facility prescription volume rose from 50,128 (PQ < 1%, AP 4%, CQ 6%, DC 53%, MQ 36%) in 2007 to 166,649 (PQ < 1%, AP 3%, CQ < 1%, DC 94%, MQ 2%) in 2011. Mefloquine use diminished in all clinics over time. The majority of military facility prescriptions originated from primary care clinics (83%); primary care clinics predominantly and increasingly prescribed DC, whereas specialty travel clinics predominantly and increasingly prescribed AP. Prescribing patterns in the MHS varied by time, practice setting, beneficiary status, and provider specialty. These changes, including among non-active duty military patients, are temporally associated with policy changes intended for the active duty force.

To determine the magnitude of Plasmodium vivax relapsing malaria in rural Amazonia, we carried out a study in four sites in northeastern Peru. Polymerase chain reaction-restriction fragment length polymorphism of PvMSP-3α and tandem repeat (TR) markers were compared for their ability to distinguish relapse versus reinfection. Of 1,507 subjects with P. vivax malaria, 354 developed > 1 episode during the study; 97 of 354 (27.5%) were defined as relapse using Pvmsp-3α alone. The addition of TR polymorphism analysis significantly reduced the number of definitively defined relapses to 26 of 354 (7.4%) (P < 0.05). Multivariate logistic regression modeling showed that the probability of having > 1 infection was associated with the following: subjects in Mazan (odds ratio [OR] = 2.56; 95% confidence interval [CI] 1.87, 3.51), 15–44 years of age (OR = 1.49; 95% CI 1.03, 2.15), traveling for job purposes (OR = 1.45; 95%CI 1.03, 2.06), and travel within past month (OR = 1.46; 95% CI 1.0, 2.14). The high discriminatory capacity of the molecular tools shown here is useful for understanding the micro-geography of malaria transmission.

Between 1993 and 2011, a total of 371 intestinal amebiasis (IA), caused by Entamoeba histolytica cases were compared with 1,113 shigellosis (randomly selected) patients of icddr,b, excluding co-infections (rotavirus and Vibrio cholerae) in two age stratums: 0–14 years of age and ≥ 15 years of age. The number of IA and shigellosis cases gradually reduced over the study period. In multivariate analysis, individuals 0–14 years of age, slum dwellers (odds ratio [OR] 3.51; 95% confidence interval [CI] 1.69–7.24; P < 0.001), red blood cell (0.44 [0.24–0.86] 0.016), fecal leukocytes (0.17 [0.07–0.33] < 0.001), and alkaline stool (0.16 [0.07–0.36] < 0.001) were independently associated with IA; and among individuals ≥ 15 years of age, living in the slum area (1.88 [1.12–3.14] 0.016), watery stool (2.21 [1.37–3.55] 0.001), use of antimicrobials before visiting hospital (0.67 [0.46–0.99] 0.047), red blood cell (0.45 [0.22–0.94] 0.036), and fecal leukocytes (0.21 [0.12–0.35] < 0.001) in stool were independently associated with IA. Socio-demographic and clinical characteristics of IA and shigellosis varied distantly from each other.

We conducted active surveillance for kala-azar and post–kala-azar dermal leishmaniasis (PKDL) in a population of 24,814 individuals. Between 2002 and 2010, 1,002 kala-azar and 185 PKDL cases occurred. Median PKDL patient age was 12 years; 9% had no antecedent kala-azar. Cases per 10,000 person-years peaked at 90 for kala-azar (2005) and 28 for PKDL (2007). Cumulative PKDL incidence among kala-azar patients was 17% by 5 years. Kala-azar patients younger than 15 years were more likely than older patients to develop PKDL; no other risk factors were identified. The most common lesions were hypopigmented macules. Of 98 untreated PKDL patients, 48 (49%) patients had resolution, with median time of 19 months. Kala-azar patients showed elevated interferon-γ (IFNγ), tumor necrosis factor-α (TNFα), and interleukin 10 (IL-10). Matrix metalloproteinase 9 (MMP9) and MMP9/tissue inhibitor of matrix metalloproteinase-1 (TIMP1) ratio were significantly higher in PKDL patients than in other groups. PKDL is frequent in Bangladesh and poses a challenge to the current visceral leishmaniasis elimination initiative in the Indian subcontinent.

The vertical transmission of leishmaniasis has been reported in species that cause visceral leishmaniasis. However, this condition has scarcely been documented in species that cause cutaneous leishmaniasis. The aim of this study was to determine experimentally whether L. mexicana is transmitted vertically. A control group of BALB/c mice and a group infected with L. mexicana were mated, the gestation was monitored, and females were killed before delivery. Four resorptions (P = 0.023) and eight fetal deaths (P = 0.010) were observed in the infected female group; furthermore, the offspring body weight of the infected group was lower than the body weight of the healthy group (P = 0.009). DNA amplification by polymerase chain reaction (PCR) revealed that all placentas and maternal spleens as well as 39 of 110 fetal spleens obtained from the offspring of infected mothers tested positive for Leishmania. In conclusion, L. mexicana is transmitted transplacentally and causes fetal death, resorption, and reduction in offspring body weight.

Treatment alternatives have seldom been evaluated in children with cutaneous leishmaniasis (CL). We examine the clinical/epidemiological profile of children with CL considering international guidelines for local treatment. Descriptive analyses were conducted using International Center for Medical Research and Training (CIDEIM) case reports of parasitologically diagnosed patients ≤ 14 years of age from 2004 to 2010. Eligibility for local treatment based on World Health Organization/Pan American Health Organization (WHO/PAHO) criteria was determined. Among 380 children, 90% presented lesions of < 3 months duration, 54% presented single lesions < 30 mm in diameter, and 45% were ≤ 5 years old. Lesions on the head and neck were more frequent among children 0–5 years, and lesions below the head/neck were more frequent among 11- to 14-year-old children (P = 0.004). Using PAHO and WHO criteria, 26% and 53% of children, respectively, were eligible for local treatment. Recommended local treatments for New World CL have potential but limited applicability in children. Individual risk–benefit assessment and effectiveness data in children may increase eligibility.

In the tropical city of Darwin, Northern Territory, Australia, dry season soil sampling cultured Burkholderia pseudomallei from 7 (70%) of 10 sports fields. However, during the 23 years of the Darwin Prospective Melioidosis Study, only 5 (0.6%) of 785 melioidosis cases have been attributed to infection from sports fields. In one soccer player with cutaneous melioidosis, B. pseudomallei cultured from the player was identical by multilocus sequence typing and multilocus variable-number tandem repeat analysis with an isolate recovered from soil at the location on the sports field where he was injured. Melioidosis is uncommon in otherwise healthy sports persons in melioidosis-endemic regions but still needs consideration in persons with abrasion injuries that involve contact with soil.

Two cases of melioidosis at a residence in rural northern Australia were linked to the unchlorinated domestic bore (automated well) water supply, which was found to have a high concentration of Burkholderia pseudomallei. Using multilocus sequence typing, clinical B. pseudomallei isolates from both cases were identical to an isolate from the bore water supply. A simple UV sterilizer reduced B. pseudomallei from the domestic water supply to undetectable levels. We have shown that UV treatment is highly effective for remediation of water contaminated with B. pseudomallei and recommend its consideration in households where individuals may be at heightened risk of contracting melioidosis.

Melioidosis is among the most common causes of septicemia in Thailand, but data on economic burden are limited. We describe the economic impact of bacteremic melioidosis hospitalizations in two Thailand provinces during 2006–2008. Costs are presented in US dollars ($1 = 30.49 Thai Baht). The average annual incidence of bacteremic melioidosis cases per 100,000 persons in Sa Kaeo and Nakhon Phanom was 4.6 and 14.4, respectively. The annual cost of bacteremic melioidosis hospitalizations from the societal perspective, including direct and indirect costs, was $152,159 in Sa Kaeo and $465,303 in Nakhon Phanom. The average cost per fatal case was $14,182 and $14,858 in Sa Kaeo and Nakhon Phanom, respectively. In addition to the high morbidity and mortality, the substantial economic burden of melioidosis further supports the need for investments to identify improved prevention and control strategies for melioidosis.

There is limited information on the prevalence of neurocysticercosis (NCC) among stroke patients, and no community-based survey has addressed this issue. We performed a 3-Phase, population-based study, to assess the prevalence and pathogenesis of stroke in a rural village of coastal Ecuador, where cysticercosis is highly endemic. Twenty stroke patients were found among 642 individuals ≥ 40 years of age. Eighteen of these patients underwent neuroimaging studies and no patient had evidence of NCC or angiitis of intracranial vessels. The serum immunoblot test for the detection of anticysticercal antibodies, performed in 15 of these 20 patients during a previous survey, were negative in 13 cases and the remaining two had a normal computed tomography of the head. This study suggests that NCC is not responsible for the increasing burden of stroke in rural areas of developing countries.

Human trichostrongylosis has been reported in Thailand. Recent reports in Lao People's Democratic Republic concerning species identification urged us to investigate species distribution in Thailand. We report eight human cases in Thailand and Lao People's Democratic Republic that were found to be infected by Trichostrongylus colubriformis and T. axei identified and confirmed by molecular techniques. This evidence is the first molecular evidence of human T. colubriformis and T. axei infection in Thailand. Infection by these two species was apparently epidemic in these areas. It is necessary to proceed with more comprehensive veterinary and epidemiologic studies to enable the practical prevention and control of this parasitic zoonosis.

Leptospirosis may be caused by > 250 Leptospira serovars. Serovar classification is a complex task that most laboratories cannot perform. We assessed the interlaboratory reproducibility of a pulsed-field gel electrophoresis (PFGE) identification technique developed by the Centers for Disease Control and Prevention (CDC). Blinded exchange of 93 Leptospiraceae strains occurred between San Antonio Military Medical Center (SAMMC) and the CDC. PFGE was performed and gel images were analyzed and compared with patterns present in each laboratory's database (CDC database: > 800 strain patterns; SAMMC database: > 300 strain patterns). Overall, 93.7% (74 of 79) of strains present in each receiving laboratory's database were correctly identified. Five isolates were misidentified, and two isolates did not match serovar PFGE patterns in the receiving laboratory's database. Patterns for these seven isolates were identical between laboratories; four serovars represented misidentified reference strains. The PFGE methodology studied showed excellent interlaboratory reproducibility, enabling standardization and data sharing between laboratories.

The home, or domicile, is the principal environment for transmission of dengue virus (DENV) between humans and mosquito vectors. Community-wide distribution of insecticide-treated curtains (ITCs), mimicking vector control program-driven interventions, has shown promise to reduce DENV infections. We conducted a Casa Segura consumer product intervention study in Mérida, Mexico to determine the potential to reduce intradomicillary DENV transmission through ITC use in individual homes. Dengue virus infections in mosquitoes and in humans were reduced in homes with ITCs in one of two study subareas. Overall, ITCs reduced intradomicillary DENV transmission; ITC homes were significantly less likely to experience multiple DENV infections in humans than NTC homes. Dengue virus–infected Aedes aegypti females were reduced within the ITC homes where curtain use was highest. Some homes yielded up to nine infected Ae. aegypti females. This study provides insights regarding best practices for Casa Segura interventions to protect homes from intradomicillary DENV transmission.