The American Journal of Tropical Medicine and Hygiene - Volume 92, Issue 1, January 2015

A 39 year-old man came to our institution because of a five-year history of a progressive painful growing mass on his left nostril, which cause airway obstruction with ulceration. Because of a suspicion of malignancy, surgery (mass resection and subtotal nasal reconstruction) was performed. Histologic samples ruled out malignancy, and tissue cultures for fungus and mycobacteria were negative, but regular aerobic cultures were positive for Klebsiella rhinoscleromatis. The patient was given a six-month regimen of ciprofloxacin, and a dramatic improvement was observed.

We present illustrative images from a Mexican 58-year-old man who had the occupation of cockfighting from childhood and presented with chronic progressive disseminated histoplasmosis with primarily cutaneous manifestations.

Improving the availability of point-of-care (POC) diagnostics for glucose is crucial in resource-constrained settings (RCS). Both hypo and hyperglycemia have an appreciable frequency in the tropics and have been associated with increased risk of deaths in pediatrics units. However, causes of dysglycemia, including hyperglycemia, are numerous and insufficiently documented in RCS. Effective glycemic control with glucose infusion and/or intensive insulin therapy can improve clinical outcomes in western settings. A non-invasive way for insulin administration is not yet available for hyperglycemia. We documented a few causes and developed simple POC treatment of hypoglycemia in RCS. We showed the efficacy of sublingual sugar in two clinical trials. Dextrose gel has been recently tested for neonate mortality. This represents an interesting alternative that should be compared with sublingual sugar in RCS. New studies had to be done to document dysglycemia mechanism, frequency and morbid-mortality, and safe POC treatment in the tropics.

Parasite antigen diversity poses an obstacle to developing an effective malaria vaccine. A protein microarray containing Plasmodium falciparum apical membrane antigen 1 (AMA1, n = 57) and merozoite surface protein 1 19-kD (MSP119, n = 10) variants prevalent at a malaria vaccine testing site in Bandiagara, Mali, was used to assess changes in seroreactivity caused by seasonal and lifetime exposure to malaria. Malian adults had significantly higher magnitude and breadth of seroreactivity to variants of both antigens than did Malian children. Seroreactivity increased over the course of the malaria season in children and adults, but the difference was more dramatic in children. These results help to validate diversity-covering protein microarrays as a promising tool for measuring the breadth of antibody responses to highly variant proteins, and demonstrate the potential of this new tool to help guide the development of malaria vaccines with strain-transcending efficacy.

Atovaquone-proguanil (AP) and artemether-lumefantrine (AL) are both treatments for uncomplicated Plasmodium falciparum malaria, but comparative clinical trials are lacking. We performed a retrospective analysis, comparing treatment failure and fever clearance time in non-immune travelers with uncomplicated P. falciparum malaria, treated with AP or AL. Sixty-nine patients were included during 2001–2013: 44 in the AP group and 25 in the AL group. Treatment failure was observed in 6 of 44 (13.6%) and 1 of 25 (4.0%) patients in the AP and AL groups, respectively. Six treatment failures were observed in travelers from West Africa. Fever clearance time was 44 ± 23 h in AL group versus 77 ± 28 h in AP group, (P < 0.001). Hospitalization time was significantly shorter in the AL group; 3.8 + 1.3 versus 5.1 + 2.8 days in the AP group (P = 0.04) In conclusion, travelers with uncomplicated P. falciparum malaria recover faster on AL than on AP. The AL should probably be the drug of choice for this population.

The primary source of malaria surveillance data in Uganda is the Health Management Information System (HMIS), which does not require laboratory confirmation of reported malaria cases. To improve data quality, an enhanced inpatient malaria surveillance system (EIMSS) was implemented with emphasis on malaria testing of all children admitted in select hospitals. Data were compared between the HMIS and the EIMSS at four hospitals over a period of 12 months. After the implementation of the EIMSS, over 96% of admitted children under 5 years of age underwent laboratory testing for malaria. The HMIS significantly overreported the proportion of children under 5 years of age admitted with malaria (average absolute difference = 19%, range = 8–27% across the four hospitals) compared with the EIMSS. To improve the quality of the HMIS data for malaria surveillance, the National Malaria Control Program should, in addition to increasing malaria testing rates, focus on linking laboratory test results to reported malaria cases.

Accurate diagnosis of glucose-6-phosphate dehydrogenase (G6PD) deficiency is required to avoid the risk of acute hemolysis associated with 8-aminoquinoline treatment. The performance of the BinaxNOW G6PD test compared with the quantitative spectrophotometric analysis of G6PD activity was assessed in 356 Plasmodium vivax-infected subjects in Brazil, Peru, Thailand, and India. In the quantitative assay, the median G6PD activity was 8.81 U/g hemoglobin (range = 0.05–20.19), with 11 (3%) subjects identified as deficient. Sensitivity of the BinaxNOW G6PD to detect deficient subjects was 54.5% (6 of 11), and specificity was 100% (345 of 345). Room temperatures inadvertently falling outside the range required to perform the rapid test (18–25°C) together with subtlety of color change and insufficient training could partially explain the low sensitivity found. Ensuring safe use of 8-aminoquinolines depends on additional development of simple, highly sensitive G6PD deficiency diagnostic tests suitable for routine use in malaria-endemic areas.

In this study, three molecular assays (real-time multiplex polymerase chain reaction [PCR], merozoite surface antigen gene [MSP]-multiplex PCR, and the PlasmoNex Multiplex PCR Kit) have been developed for diagnosis of Plasmodium species. In total, 52 microscopy-positive and 20 malaria-negative samples were used in this study. We found that real-time multiplex PCR was the most sensitive for detecting P. falciparum and P. knowlesi. The MSP-multiplex PCR assay and the PlasmoNex Multiplex PCR Kit were equally sensitive for diagnosing P. knowlesi infection, whereas the PlasmoNex Multiplex PCR Kit and real-time multiplex PCR showed similar sensitivity for detecting P. vivax. The three molecular assays displayed 100% specificity for detecting malaria samples. We observed no significant differences between MSP-multiplex PCR and the PlasmoNex multiplex PCR kit (McNemar's test: P = 0.1489). However, significant differences were observed comparing real-time multiplex PCR with the PlasmoNex Multiplex PCR Kit (McNemar's test: P = 0.0044) or real-time multiplex PCR with MSP-multiplex PCR (McNemar's test: P = 0.0012).

Malaria is responsible for close to 1 million deaths each year, mostly among African children. Red blood cells (RBCs) of children with severe malarial anemia show loss of complement regulatory proteins such as complement receptor 1 (CR1). We carried out this study to identify socio-economic, environmental, and biological factors associated with the loss of RBC CR1. A cross-sectional study was conducted in a malaria holoendemic area of western Kenya. Twelve socioeconomic, environmental, and biological factors were examined for a relationship with RBC CR1 level using bivariate linear regression followed by creation of a multivariate linear regression model. A significant positive relationship between RBC CR1 level and use of mosquito countermeasures was found. However, there was no evidence of a significant relationship between RBC CR1 level and malaria infection or parasitemia level. Reducing mosquito exposure may aid in the prevention of severe malarial anemia by reducing the number of infections and thus preserving RBC CR1.

Approximately 8 million people have Trypanosoma cruzi infection, and nearly 30% will manifest Chagas cardiomyopathy (CC). Identification of reliable early indicators of CC risk would enable prioritization of treatment to those with the highest probability of future disease. Serum markers and electrocardiogram (EKG) changes were measured in 68 T. cruzi-infected individuals in various stages of cardiac disease and 17 individuals without T. cruzi infection or cardiac disease. T. cruzi-infected individuals were assigned to stage A (normal EKG/chest x-ray [CXR]), B (abnormal EKG/normal CXR), or C (abnormal EKG/cardiac structural changes). Ten serum markers were measured using enzyme-linked immunosorbent assay (ELISA)/Luminex, and QRS scores were calculated. Higher concentrations of transforming growth factor-β1 (TGFβ1), and TGFβ2 were associated with stage B compared with stage A. Matrix Metalloproteinase 2 (MMP2), Tissue Inhibitors of MMP 1, QRS score, and Brain Natriuretic Protein rose progressively with increasing CC severity. Elevated levels of several markers of cardiac damage and inflammation are seen in early CC and warrant additional evaluation in longitudinal studies.

Cryptosporidium is an important diarrhea-associated pathogen, however the correlation between parasite burden and diarrhea severity remains unclear. We studied this relationship in 10 experimentally infected calves using immunofluorescence microscopy and real-time polymerase chain reaction (qPCR) (N = 124 fecal samples). The qPCR data were corrected for extraction/amplification efficiency and gene copy number to generate parasite counts. The qPCR and microscopic oocyst quantities exhibited significant correlation (R2 = 0.33, P < 0.05), however qPCR had increased sensitivity. Upon comparison with diarrhea severity scores (from 0 to 3), a PCR-based count of ≥ 2.6 × 105 parasites or an immunofluorescence microscopy count of ≥ 4.5 × 104 oocysts were discriminatory predictors of moderate-to-severe diarrhea (versus no-to-mild diarrhea), with accuracies and predictive values of 72–82%. In summary, a quantitative approach for Cryptosporidium can refine predictive power for diarrhea and appears useful for distinguishing clinical cryptosporidiosis versus subclinical infection.

Although Cryptosporidium parvum and C. hominis cause the majority of human cryptosporidiosis cases, other Cryptosporidium species are also capable of infecting humans, particularly when individuals are immunocompromised. Ten C. muris cases have been reported, primarily in human immunodeficiency virus (HIV) -positive patients with diarrhea. However, asymptomatic cases were reported in two HIV-negative children, and in another case, age and immune status were not described. This study examines the infectivity of C. muris in six healthy adults. Volunteers were challenged with 105 C. muris oocysts and monitored for 6 weeks for infection and/or illness. All six patients became infected. Two patients experienced a self-limited diarrheal illness. Total oocysts shed during the study ranged from 6.7 × 106 to 4.1 × 108, and the number was slightly higher in volunteers with diarrhea (2.8 × 108) than asymptomatic shedders (4.4 × 107). C. muris-infected subjects shed oocysts longer than occurred with other species studied in healthy volunteers. Three volunteers shed oocysts for 7 months. Physical examinations were normal, with no reported recurrence of diarrhea or other gastrointestinal complaints. Two persistent shedders were treated with nitazoxanide, and the infection was resolved. Thus, healthy adults are susceptible to C. muris, which can cause mild diarrhea and result in persistent, asymptomatic infection.

Taenia solium taeniasis/cysticercosis is an important public health problem occurring mainly in developing countries. This work aimed to study the determinants of human T. solium infections in the Eastern province of Zambia and rank them in order of importance. A household (HH)-level questionnaire was administered to 680 HHs from 53 villages in two rural districts and the taeniasis and cysticercosis status determined. A classification tree model (CART) was used to define the relative importance and interactions between different predictor variables in their effect on taeniasis and cysticercosis. The Katete study area had a significantly higher taeniasis and cysticercosis prevalence than the Petauke area. The CART analysis for Katete showed that the most important determinant for cysticercosis infections was the number of HH inhabitants (6 to 10) and for taeniasis was the number of HH inhabitants > 6. The most important determinant in Petauke for cysticercosis was the age of head of household > 32 years and for taeniasis it was age < 55 years. The CART analysis showed that the most important determinant for both taeniasis and cysticercosis infections was the number of HH inhabitants (6 to 10) in Katete district and age in Petauke. The results suggest that control measures should target HHs with a high number of inhabitants and older individuals.

Calcified neurocysticercosis has been associated with hippocampal atrophy in patients with refractory epilepsy, but the relevance of this association in the population at large is unknown. We assessed calcified cysticerci and its association with hippocampal atrophy in elderly persons living in Atahualpa, an Ecuadorian village endemic for neurocysticercosis. All Atahualpa residents ≥ 60 years of age were invited to undergo computed tomography/magnetic resonance imaging for neurocysticercosis detection. Twenty-eight (11%) out of 248 enrolled persons had calcified cysticerci (case-patients) and were matched 1:1 by age, sex, and years of education to individuals without neurocysticercosis on computed tomography/magnetic resonance imaging (controls). Four case-patients and none of the controls had epilepsy (P = 0.134). Cognitive performance was similar across both groups. The Scheltens' medial temporal atrophy scale was used for hippocampal rating in case-patients and matched controls without neurocysticercosis. Mean score in the Scheltens' scale was higher in case-patients than in controls (P < 0.001). Atrophic hippocampi were noticed in 19 case-patients and five controls (P = 0.003). Atrophy was bilateral in 11 case-patients and unilateral in eight. All case-patients with unilateral hippocampal atrophy had at least one ipsilateral calcification. This study shows an association between calcified cysticerci and hippocampal atrophy and raises the possibility of an inflammation-mediated hippocampal damage as the responsible mechanism for these findings.

Dengue is an acute febrile illness caused by any of four mosquito-transmitted dengue virus (DENV) types. Dengue is endemic in Jamaica, where an epidemic occurred in 2012. An investigation was conducted by multiple agencies for 66 missionaries traveling from nine US states to Jamaica after 1 missionary from the group was confirmed to have dengue. Travelers were offered diagnostic testing, and a survey was administered to assess knowledge, behaviors, and illness. Of 42 survey respondents, 9 (21%) respondents reported an acute febrile illness during or after travel to Jamaica. Of 15 travelers that provided serum specimens, 4 (27%) travelers had detectable anti-DENV immunoglobulin M antibody, and 1 traveler also had DENV-1 detected by reverse transcriptase polymerase chain reaction. Recent or past infection with a DENV was evident in 93% (13 of 14) missionaries with available sera. No behavioral or demographic factors were significantly associated with DENV infection. This investigation shows that even trips of short duration to endemic areas present a risk of acquiring dengue.

Because the prevalence of dengue fever in urban settings in Papua New Guinea is unknown, we investigated the presence of dengue using the NS1 antigen test in an outpatient-based prospective observational study at Port Moresby General Hospital. Of 140 patients with acute febrile illnesses, dengue fever was diagnosed in 14.9% (20 of 134; 95% confidence interval [95% CI] = 9.6–22.4). Malaria (2 of 137; 1.5%; 95% CI = 0.3–5.7), chikungunya (3 of 140; 2.1%; 95% CI = 0.6–6.6), and bacterial bloodstream infections (0 of 80; 0%; 95% CI = 0–5.7) were uncommon. Dengue fever should no longer be considered rare in Papua New Guinea.

Among 1,076 dengue patients, 9 patients with rhabdomyolysis and 1,067 patients without rhabdomyolysis (controls) were retrospectively analyzed. Of nine patients with rhabdomyolysis, the most commonly reported symptom other than fever was myalgia; dengue hemorrhagic fever (DHF) was found in seven cases, and acute kidney injury was found in six cases. Furthermore, one (11.1%) patient died. The median duration from hospital admission to rhabdomyolysis diagnosis was 3 days. Patients with rhabdomyolysis had higher age, proportion of men, prevalence of hypertension, frequency of myalgia, and incidences of DHF, pleural effusion, and acute kidney injury than controls. Multivariate analysis showed that hypertension (odds ratio [OR] = 14.270), myalgia (OR = 20.377), and acute kidney injury (OR = 65.547) were independent risk factors for rhabdomyolysis. Comparison of cytokine/chemokine concentrations in 101 DHF patients, including those with (N = 4) and without (N = 97) rhabdomyolysis, showed that interleukin-6 and tumor necrosis factor-α levels were significantly increased in the former.

Chikungunya virus is an emerging threat to the United States because humans are amplifying hosts and competent mosquito vectors are present in many regions of the country. We identified laboratory-confirmed chikungunya virus infections with diagnostic testing performed in the United States from 2010 through 2013. We described the epidemiology of these cases and determined which were reported to ArboNET. From 2010 through 2013, 115 laboratory-confirmed chikungunya virus infections were identified. Among 55 cases with known travel history, 53 (96%) reported travel to Asia and 2 (4%) to Africa. No locally-acquired infections were identified. Six patients had detectable viremia after returning to the United States. Only 21% of identified cases were reported to ArboNET, with a median of 72 days between illness onset and reporting. Given the risk of introduction into the United States, healthcare providers and public health officials should be educated about the recognition, diagnosis, and timely reporting of chikungunya virus disease cases.

Sylvatic arboviruses have been isolated in Senegal over the last 50 years. The ecological drivers of the pattern and frequency of virus infection in these species are largely unknown. We used time series analysis and Bayesian hierarchical count modeling on a long-term arbovirus dataset to test associations between mosquito abundance, weather variables, and the frequency of isolation of dengue, yellow fever, chikungunya, and Zika viruses. We found little correlation between mosquito abundance and viral isolations. Rainfall was a negative predictor of dengue virus (DENV) isolation but a positive predictor of Zika virus isolation. Temperature was a positive predictor of yellow fever virus (YFV) isolations but a negative predictor of DENV isolations. We found slight interference between viruses, with DENV negatively associated with concurrent YFV isolation and YFV negatively associated with concurrent isolation of chikungunya virus. These findings begin to characterize some of the ecological associations of sylvatic arboviruses with each other and climate and mosquito abundance.