Cassidy W. Claassen

Return of Widespread Chloroquine-Sensitive Plasmodium falciparum to Malawi

BACKGROUND The return of chloroquine-sensitive Plasmodium falciparum to the limited area of Blantyre, Malawi, has been well demonstrated in several studies. METHODS To characterize chloroquine susceptibility over a wide geographic area, infants and children aged 6-59 months were selected using 2-stage cluster sampling in 8 Malawian districts. Pyrosequencing of the pfcrt gene codon 76 region was performed for children with asexual parasitemia. RESULTS Of 7145 children, 1150 had microscopic asexual parasitemia, and sequencing was performed in 685, of whom 1 had a chloroquine-resistant genotype. CONCLUSIONS Systematic countrywide sampling demonstrates that the chloroquine pfcrt genotype has reached near-fixation, raising the possibility of reintroducing chloroquine for malaria prevention and treatment.

The effect of a bidirectional exchange on faculty and institutional development in a global health collaboration.

Purpose The MUYU Collaboration is a partnership between Mulago Hospital-Makerere University College of Health Sciences (M-MakCHS), in Kampala, Uganda, and the Yale University School of Medicine. The program allows Ugandan junior faculty to receive up to 1 year of subspecialty training within the Yale hospital system. The authors performed a qualitative study to assess the effects of this program on participants, as well as on M-MakCHS as an institution. Methods Data was collected via semi-structured interviews with exchange participants. Eight participants (67% of those eligible as of 4/2012) completed interviews. Study authors performed data analysis using standard qualitative data analysis techniques. Results Analysis revealed themes addressing the benefits, difficulties, and opportunities for improvement of the program. Interviewees described the main benefit of the program as its effect on their fund of knowledge. Participants also described positive effects on their clinical practice and on medical education at M-MakCHS. Most respondents cited financial issues as the primary difficulty of participation. Post-participation difficulties included resource limitations and confronting longstanding institutional and cultural habits. Suggestions for programmatic improvement included expansion of the program, ensuring appropriate management of pre-departure expectations, and refinement of program mentoring structures. Participants also voiced interest in expanding post-exchange programming to ensure both the use of and the maintenance of new capacity. Conclusions The MUYU Collaboration has benefitted both program participants and M-MakCHS, though these benefits remain difficult to quantify. This study supports the assertion that resource-poor to resource-rich exchanges have the potential to provide significant benefits to the resource-poor partner.

Discordance Between CD4+ T-Lymphocyte Counts and Percentages in HIV-Infected Persons With Liver Fibrosis

BACKGROUND Cirrhosis of the liver can induce splenic sequestration of peripheral blood cells, recently suggested to reduce the number but not percentage of circulating CD4(+) T cells in persons uninfected with human immunodeficiency virus (HIV). We investigated whether earlier stages of liver fibrosis prior to cirrhosis were associated with discordance between CD4 count (CD4N) and CD4 percentage (CD4%) in HIV-infected patients. METHODS In cross-sectional analysis of 287 HIV-infected participants of the AIDS Linked to the Intravenous Experience cohort, we evaluated CD4N, CD4%, and transient elastography staging of liver fibrosis. High CD4(+) lymphocyte discordance was defined as higher CD4% relative to CD4N based on accepted clinical cutoffs; multivariable logistic regression was used to determine covariates associated with discordance. RESULTS Of 287 participants, 99 (34.4%) had high CD4(+) discordance, which increased to 76% of 114 participants with marked lymphopenia (total lymphocyte count [TLC] ≤1200 cells/μL). In multivariable analysis, the odds of having high CD4(+) discordance was increased in persons with significant liver fibrosis compared to those without fibrosis (odds ratio, 1.69; 95% confidence interval [CI], .95-2.96); the odds ratio of discordance increased to 2.66 (95% CI, 1.11-6.40) among the subset of participants with TLC ≤1200 cells/μL. The odds for discordance associated with cirrhosis were of similar magnitude as those observed with significant fibrosis. CONCLUSIONS In HIV-infected persons, liver fibrosis is associated with discordant peripheral CD4(+) lymphocyte results, especially in the setting of marked lymphopenia. Clinicians should also consider CD4% when interpreting absolute CD4(+) counts of HIV-infected persons with known or suspected liver disease, particularly if TLC is <1200 cells/μL.

Chloroquine-Azithromycin Combination Antimalarial Treatment Decreases Risk of Respiratory- and Gastrointestinal-Tract Infections in Malawian Children

BACKGROUND Chloroquine-azithromycin is being evaluated as combination therapy for malaria. It may provide added benefit in treating or preventing bacterial infections that occur in children with malaria. OBJECTIVE We aim to evaluate the effect of treating clinical malaria with chloroquine-azithromycin on the incidence of respiratory-tract and gastrointestinal-tract infections compared to treatment with chloroquine monotherapy. METHODS We compared the incidence density and time to first events of respiratory-tract and gastrointestinal-tract infections among children assigned to receive chloroquine-azithromycin or chloroquine for all symptomatic malaria episodes over the course of 1 year in a randomized longitudinal trial in Blantyre, Malawi. RESULTS The incidence density ratios of total respiratory-tract infections and gastrointestinal-tract infections comparing chloroquine-azithromycin to chloroquine monotherapy were 0.67 (95% confidence interval [CI], .48, .94) and 0.74 (95% CI, .55, .99), respectively. The time to first lower-respiratory-tract and gastrointestinal-tract infections were significantly longer in the chloroquine-azithromycin arm compared to the chloroquine arm (P = .04 and P = .02, respectively). CONCLUSIONS Children treated routinely with chloroquine-azithromycin had fewer respiratory and gastrointestinal-tract infections than those treated with chloroquine alone. This antimalarial combination has the potential to reduce the burden of bacterial infections among children in malaria-endemic countries.

Penetrating cardiac injury: Think outside the box

Although infrequent penetrating cardiac wounds are often lethal, cardiac injury occurs in 6.4% of penetrating chest wounds with a resultant 21.9% mortality.1 A precordial wound (in the box) suggests the possibility of a cardiac injury, and rapid diagnosis and repair improves survival.2 Echocardiography is a useful modality to diagnose penetrating cardiac injury and tamponade.3 This report describes two cases of penetrating cardiac injury with entrance wounds “outside the box” and illustrates the utility of echocardiography.

Active Tuberculosis Case Finding in Port-au-Prince, Haiti: Experiences, Results, and Implications for Tuberculosis Control Programs

Background. Haiti has the highest tuberculosis (TB) prevalence in the Americas with 254 cases per 100,000 persons. Case detection relies on passive detection and TB services in many regions suffer from poor diagnostic and clinical resources. Methods. Mache Chache (“Go and Seek”) was a TB REACH Wave 3 funded TB case finding project in Port-au-Prince between July 2013 and September 2014, targeting four intervention areas with insufficient TB diagnostic performance. Results. Based on a verbal symptom screen emphasizing the presence of cough, the project identified 11,150 (11.75%) of all screened persons as TB subjects and 2.67% as smear-positive (SS+) TB cases. Enhanced case finding and strengthening of laboratory services led to a 59% increase in bacteriologically confirmed cases in the evaluation population. In addition, smear grades dropped significantly, suggesting earlier case detection. Xpert® MTB/RIF was successfully introduced and improved TB diagnosis in HIV-infected, smear-negative clinic patients, but not in HIV-negative, smear-negative TB suspects in the community. However, the number needed to screen for one additional SS+ case varied widely between clinic and community screening activities. Conclusion. Enhanced and active TB case finding in Haiti can improve TB diagnosis and care. However, screening algorithms have to be tailored to individual settings, necessitating long-term commitment.

The Arc of Human Immunodeficiency Virus Capacity Development: Insights from a Decade of Partnership for Medical Education in Zambia

AbstractZambia and other sub-Saharan nations suffer from a critical shortage of trained health-care professionals to combat the human immunodeficiency virus/acquired immunodeficiency syndrome crisis. The University of Maryland and the Zambian Ministry of Health have partnered over the past decade to develop health-care capacity among physicians, nurses, and community health workers. We describe novel interventions to train health-care workers at all levels and argue that our collaboration represents a successful model for such partnerships between western medical institutions and African governmental health agencies.

Photo Quiz: Fungal sinusitis in a 75-year-old neutropenic cancer patient.

Diagnosis: Invasive fungal sinusitis due to Curvularia species. This patient described had a prolonged neutropenia, with upper respiratory symptoms and sinus mucosal thickening. Aspergillosis and mucormycosis are common causes of fungal sinusitis in this immunocompromised population, but Curvularia and other dematiaceous molds (DMs) can occur less frequently. Curvularia has been known to cause sinonasal, pulmonary, skin, and intracranial infections, keratitis, and disseminated disease in the immunocompromised host [1, 2]. DMs are ubiquitous organisms, with >150 species and 70 genera [3]. The distinguishing characteristic common to these diverse species is the presence of melanin in their cell walls. Other DMs commonly associated with clinical syndromes of phaeohyphomycosis include Bipolaris and Exserohilum, among others, and are classified according to conidia/conidiophore morphology [2].Multiple species of Curvularia have been implicated in human disease with recent molecular typing identifying several new species [4]; however, C. lunata is the most commonly reported clinical species [3]. In the laboratory, colonies grow rapidly on potato dextrose agar, developing the characteristic grayish-black appearance. DMs do not have characteristic growth on Sabouraud dextrose agar, a common primary fungal media [2].Tape mount with lactophenol cotton blue of a colony (Figure 1) revealed characteristic curved macroconidia with transverse septae and an enlarged darker central cell causing the bent appearance (left arrow). In the background, septate hyphae are visible as well (right arrow). Darkly pigmented, bent, or knobby (sympodial Figure 2. Histopathology of anterior aspect of middle turbinate. A, Hematoxylin–eosin stain (×1000 magnification with oil). B, Grocott methenamine silver stain (×200 magnification). The dark brown melanin pigment in the cell wall of the hyphae (arrows). Figure 1. Tape mount with lactophenol cotton blue of mold colonies showing curved macroconidia and septate hyphae. Characteristic curved macroconidia with transverse septae and an enlarged darker central cell causing the bent appearance (left arrow). In the background, septate hyphae are visible as well (right arrow).