The American Journal of Tropical Medicine and Hygiene - Online First

The sale of artemisinin-based combination therapy (ACT) by private licensed chemical shops (LCS) without testing is contrary to current policy recommendations. This study assessed the accuracy and perception of test-based management of malaria using malaria rapid diagnostic test (mRDT) kits at private LCS in two predominantly rural areas in the middle part of Ghana. Clients presenting at LCS with fever or other signs and symptoms suspected to be malaria in the absence of signs of severe malaria were tested with mRDT by trained attendants and treated based on the national malaria treatment guidelines. Using structured questionnaires, exit interviews were conducted within 48 hours and a follow-up interview on day 7 (±3 days). Focus group discussions and in-depth interviews were also conducted to assess stakeholders’ perception on the use of mRDT at LCS. About 79.0% (N = 1,797) of clients reported with a fever. Sixty-six percent (947/1,426) of febrile clients had a positive mRDT result. Eighty-six percent (815/947) of clients with uncomplicated malaria were treated with the recommended ACT. About 97.8% (790/808) of clients with uncomplicated malaria treated with ACT were reported to be well by day 7. However, referral for those with negative mRDT results was very low (4.1%, 27/662). A high proportion of clients with a positive mRDT result received the recommended malaria treatment. Test-based management of malaria by LCS attendants was found to be feasible and acceptable by the community members and other stakeholders. Successful implementation will however require effective referral, supervision and quality control systems.

Isolated renal mucormycosis in immunocompetent hosts is a rare entity. We present the largest case series of isolated renal mucormycosis in immunocompetent hosts. Retrospective data of isolated renal mucormycosis from March 2012 to June 2017 were reviewed. Fifteen patients of isolated renal mucormycosis were identified. Contrast-enhanced computed tomography scan showed enlarged globular kidneys with decreased or patchy enhancement, perinephric stranding, and thickened Gerota’s fascia in all patients. Ten patients with unilateral involvement underwent nephrectomy, and two of four patients with bilateral renal mucormycosis underwent bilateral nephrectomy. Two patients were managed with intravenous antifungal therapy alone. Overall, the mortality rate in our series was 40% (6/15). Isolated renal mucormycosis in healthy immunocompetent hosts is an emerging new entity. Prompt diagnosis based on the characteristic clinical and radiological picture, and starting high-dose antifungal therapy at least 24 hours before surgical debridement offer the best chance of survival in these patients.

The dengue situation in the urban setting of Hanoi city, Vietnam, is emerging, focusing on inner districts. Previous studies showed that a dengue vector control program in Hanoi was not effective because of the lack of adequate engagement of the local government authorities, health sector, and community. This implementation research aimed to explore barriers to implementing community engagement in a dengue vector control program in an urban district of Hanoi city. Ten in-depth interviews and 14 focus group discussions were conducted at Lang Thuong, Khuong Thuong, Tho Quan, and Kim Lien wards in Dong Da district, Hanoi city. Data collection was implemented from April to June 2017. All discussions were recorded and transcribed verbatim. Data were analyzed using the content analysis approach. Secondary data from the dengue vector control program reports were used to support the qualitative evidence. We found that the barriers to implementing effective community engagement were as follows: 1) lack of interest and an attitude of dependency on action from the health sector of local people’s committee, 2) lack of enthusiasm of mass organizations and community leaders, 3) overburdened workloads and lack of communication skills from health sector, 4) low awareness and readiness from community, 5) lack of detailed policy guidelines and low enforcement of related policy, and 6) limited budget. Recommended actions should be made to improve the community engagement in the current resource-limited context of Vietnam by both top-down and bottom-up approaches.

Type 2 reaction (T2R) or erythema nodosum leprosum (ENL), a sudden episode of acute inflammation predominantly affecting lepromatous leprosy patients (LL), characterized by a reduced cellular immune response. This possibly indicates a close relationship between the onset of T2R and the altered frequency, and functional activity of T lymphocytes, particularly of memory subsets. This study performed ex vivo and in vitro characterizations of T cell blood subpopulations from LL patients with or without T2R. In addition, the evaluation of activity of these subpopulations was performed by analyzing the frequency of these cells producing IFN-γ, TNF, and IL-10 by flow cytometry. Furthermore, the expression of transcription factors, for the differentiation of T cells, were analyzed by quantitative real-time polymerase chain reaction. Our results showed an increased frequency of CD8+/TNF+ effector memory T cells (TEM) among T2Rs. Moreover, there was evidence of a reduced frequency of CD4 and CD8+ IFN-γ–producing cells in T2R, and a reduced expression of STAT4 and TBX21. Finally, a significant and positive correlation between bacillary index (BI) of T2R patients and CD4+/TNF+ and CD4+/IFN-γ+ T cells was observed. Thus, negative correlation between BI and the frequency of CD4+/IL-10+ T cells was noted. These results suggest that CD8+/TNF+ TEM are primarily responsible for the transient alteration in the immune response to Mycobacterium leprae in ENL patients. Thus, our study will provide a better understanding of pathogenic mechanisms and will lead to new promising therapeutic choices.

The current strategy used by many funding agencies for determining how money is spent on research to help prevent infectious disease outbreaks is based on pathogen-specific priority lists. Listing disease threats provides focus for business and research planning conducive to focused goals of developing a drug, or a vaccine, or other particular product. But, this singular type of focus has consequences. This perspective explores the consequences of lists, and describes how parallel programming independent of disease lists that focus on what we need to do to prevent and mitigate emerging disease risks may provide benefits out of reach of a singular focus on what products we need to have.

Acute undifferentiated febrile illness (AUFI) has been a diagnostic dilemma in the tropics. Without accurate point-of-care tests, information on local pathogens and clinical parameters is essential for presumptive diagnosis. A prospective hospital-based study was conducted at the Bangkok Hospital for Tropical Diseases from 2013 to 2015 to determine common etiologies of AUFI. A total of 397 adult AUFI cases, excluding malaria by blood smear, were enrolled. Rapid diagnostic tests for tropical infections were performed on admission, and acute and convalescent samples were tested to confirm the diagnosis. Etiologies could be identified in 271 (68.3%) cases. Dengue was the most common cause, with 157 cases (39.6%), followed by murine typhus (20 cases; 5.0%), leptospirosis (16 cases; 4.0%), influenza (14 cases; 3.5%), and bacteremia (six cases; 1.5%). Concurrent infection by at least two pathogens was reported in 37 cases (9.3%). Furthermore, characteristics of dengue and bacterial infections (including leptospirosis and rickettsioses) were compared to facilitate dengue triage, initiate early antibiotic treatment, and minimize unnecessary use of antibiotics. In conclusion, dengue was the most common pathogen for AUFI in urban Thailand. However, murine typhus and leptospirosis were not uncommon. Empirical antibiotic treatment using doxycycline or azithromycin might be more appropriate, but cost–benefit studies are required. Physicians should recognize common causes of AUFI in their localities and use clinical and laboratory clues for provisional diagnosis to provide appropriate treatment while awaiting laboratory confirmation.

This study was conducted to find the burden of dengue virus (DENV) and Japanese encephalitis virus (JEV) among children under the age of 13, who presented with acute encephalitis syndrome at Mandalay Children Hospital in Myanmar in 2013. Molecular and serological investigations were performed on 123 cerebrospinal fluid (CSF) samples collected from these patients. By neutralization tests and/or virus isolation, four (3.3%) JEV- and one DENV-associated encephalitis cases (0.8%) were confirmed. Antibody titer against JEV Genotype 3 was the highest among the laboratory-confirmed JEV cases. One strain of DENV-1 with Genotype 1 was isolated from the CSF sample of the dengue encephalitis patient; this was similar to the virus circulating in the study area and neighboring countries. This study shows that flaviviruses are important pathogens causing encephalitis in Myanmar. Active disease surveillance, vector control, and vaccination programs should be enforced to reduce the morbidity and mortality caused by flavivirus encephalitis.

A 23-year-old recent emigrant from Afghanistan presented in August 2017 with severe wheezing and dyspnea that required hospital admission. Her illness was associated with marked peripheral blood eosinophilia (9,900–15,600/µL; 45.2–68%), as well as mild nausea, epigastric pain, and decreased appetite. She had lived until 3 months earlier in close proximity to cattle in her home in Kabul and did not recall eating watercress or other leafy plants associated with Fasciola hepatica transmission. Computerized tomography scanning showed bilateral ground-glass lung consolidations and multiple distinctive hypo-attenuating linear, tubuliform, and nodular liver lesions, including a large subcapsular hematoma. Numerous tests for rheumatological and malignant disorders were negative. Fasciola hepatica infestation was suspected on epidemiological, clinical, and radiographic grounds, and was confirmed by immunoblotting at the Centers for Disease Control (CDC). Multiple stool ova and parasite examinations were negative and endoscopic retrograde cholangiopancreatography did not identify trematodes. Her acute respiratory illness resolved with asthma-targeted therapies and her eosinophilia resolved with triclabendazole, which was obtained from CDC via an FDA Investigational New Drug application. Fascioliasis is uncommon in the United States, but the prolonged warfare and civil strife in Afghanistan and adjacent areas may lead to increased incidence outside the endemic region. Her case also demonstrates how hepatic imaging features of fascioliasis can be pathognomonic in clinical scenarios with eosinophilia and appropriate epidemiology and clinical features. We also highlight her relatively unusual presentation with symptoms of Loeffler-like syndrome alone.

Maternal infection during pregnancy can have lasting effects on neurodevelopment, but the impact of malaria in pregnancy on child neurodevelopment is unknown. We present a case of a 24-year-old gravida three woman enrolled at 14 weeks 6 days of gestation in a clinical trial evaluating malaria prevention strategies in pregnancy. She had two blood samples test positive for Plasmodium falciparum using loop-mediated isothermal amplification before 20 weeks of gestation. At 31 weeks 4 days of gestation, the woman presented with preterm premature rupture of membranes, and the twins were delivered by cesarean section. Twin A was 1,920 g and Twin B was 1,320 g. Both placentas tested negative for malaria by microscopy, but the placenta of Twin B had evidence of past malaria by histology. The twins’ development was assessed using the Bayley Scales of Infant and Toddler Development–Third Edition. At 1 year chronologic age, Twin B had lower scores across all domains (composite scores: cognitive, Twin A [100], Twin B [70]; motor, Twin A [88], Twin B [73]; language, Twin A [109], Twin B [86]). This effect persisted at 2 years chronologic age (composite scores: cognitive, Twin A [80], Twin B [60]; motor, Twin A [76], Twin B [67]; language, Twin A [77], Twin B [59]). Infant health was similar over the first 2 years of life. We report differences in neurodevelopmental outcomes in placental malaria-discordant dizygotic twins. Additional research is needed to evaluate the impact of placental malaria on neurodevelopmental complications. Trial registration number: ClinicalTrials.gov number, NCT02163447. Registered: June 2014, https://clinicaltrials.gov/ct2/show/NCT02163447.