The American Journal of Tropical Medicine and Hygiene - Volume 87, Issue 1, 2012

Isolated tuberculosis of the pancreas is rare even in developing countries where abdominal tuberculosis continues to be prevalent. We present a case of pancreatic tuberculosis in an immunocompetent male with confounding imaging findings and non-contributory clinical details.

Undergraduate public health and global health studies are usually found at universities with graduate programs in the disciplines. Following the experience of teaching a short course in global health within the liberal arts, we reviewed global and public health offerings at 50 liberal arts colleges for the 2009–2010 academic year. Forty-two percent had a track, concentration, or program, and 30% had global or public health student organizations. All colleges listed at least one course in the fields, with the highest number in the social sciences. However, many colleges had not coordinated them into a theme. Values of a liberal arts education are found in the study of global and public health: social responsibility, critical thinking, ethical reasoning, and knowledge of the wider world. We propose identifying these programs within the undergraduate liberal arts as global public health. Capturing interest in global public health will enhance the curriculum and student experience.

In this day and age, when the world is so fluid with regard to news and information, the knowledge that unnecessary deaths are occurring and that health care lags so far behind in some regions cannot be ignored. From the standpoint of basic human rights, suffering and inequity cannot be tolerated.

Williams College student during a global health short course

How does specific information about contamination in a household's drinking water affect water handling behavior? We randomly split a sample of households in rural Andhra Pradesh, India. The treatment group observed a contamination test of the drinking water in their own household storage vessel; while they were waiting for their results, they were also provided with a list of actions that they could take to remedy contamination if they tested positive. The control group received no test or guidance. The drinking water of nearly 90% of tested households showed evidence of contamination by fecal bacteria. They reacted by purchasing more of their water from commercial sources but not by making more time-intensive adjustments. Providing salient evidence of risk increases demand for commercial clean water.

Plasmodium falciparum resistance to artemisinins by delayed parasite clearance is present in Southeast Asia. Scant data on parasite clearance after artemisinins are available from Africa, where transmission is high, burden is greatest, and artemisinin use is being scaled up. Children 1–10 years of age with uncomplicated malaria were treated with 7 days of artesunate and followed for 28 days. Blood smears were done every 8 hours until negative by light microscopy. Results were compared with a similar study conducted in the same village in 2002–2004. The polymerase chain reaction-corrected cure rate was 100%, identical to 2002–2004. By 24 hours after treatment initiation, 37.0% of participants had cleared parasitemia, compared with 31.9% in 2002–2004 (P = 0.5). The median parasite clearance time was 32 hours. Only one participant still had parasites at 48 hours and no participant presented parasitemia at 72 hours. Artesunate was highly efficacious, with no evidence of delayed parasite clearance. We provide baseline surveillance data for the emergence or dissemination of P. falciparum resistance in sub-Saharan Africa.

Plasmodium falciparum and human immunodeficiency virus (HIV) are both risk factors for low birth weight (LBW) and maternal anemia, and they may interact to increase risk of adverse pregnancy outcomes. In 2005 and 2006, we followed 831 pregnant women attending antenatal care clinics in southern Malawi through delivery. HIV was associated with increased risk of LBW (adjusted prevalence ratio [PRadj] = 3.08, 95% confidence interval [CI] = 1.40, 6.79). Having greater than or equal to three episodes of peripheral parasitemia was also associated with increased risk of LBW (PRadj = 2.68, 95% CI = 1.06, 6.79). Among multigravidae, dual infection resulted in 9.59 (95% CI = 2.51, 36.6) times the risk of LBW compared with uninfected multigravidae. HIV infection and placental parasitemia were each associated with increased risk of anemia. Thus, HIV infection and parasitemia are important independent risk factors for adverse pregnancy outcomes. Among multigravidae, HIV infection and placental parasitemia may interact to produce an impact greater than the sum of their independent effects.

The pharmacokinetic properties of piperaquine were investigated in 12 pregnant and 12 well-matched, non-pregnant women receiving a three-day oral fixed dose combination regimen of dihydroartemisinin and piperaquine for treatment of uncomplicated Plasmodium falciparum at New Halfa Hospital in eastern Sudan. Frequent venous plasma samples were drawn from the patients over a 63-day period and a complete concentration–time profile was collected for 7 pregnant and 11 non-pregnant patients. Piperaquine was quantified using a liquid chromatography–mass spectrometry/mass spectrometry method. Pregnant women had a significantly higher total drug exposure (median area under the curve [range] = 1,770 [1,200–5,600] hr × ng/mL versus 858 [325–2,370] hr × ng/mL; P = 0.018) and longer time to maximal concentration (4.00 [1.50–4.03] hr versus 1.50 [0.500–8.00] hr; P = 0.02) after the first dose compared with non-pregnant women. There was no other significant difference observed in piperaquine pharmacokinetics between pregnant and non-pregnant women, including no difference in total drug exposure or maximum concentration. The overall pharmacokinetic properties of piperaquine in this study were consistent with previously published reports in non-pregnant patients.

Records of 3,449 patients admitted to Karitas Hospital at Waitabula in eastern Indonesia with microscopy-confirmed malaria through 2008 and 2009 were systematically reviewed. Falciparum, vivax, and mixed species malaria occurred among 1,541, 1,837, and 71 admissions, respectively. Among these, 400 (26%), 199 (11%), and 15 (21%) had serious illness. Fatalities occurred in 46 (12%), 18 (9%), and 2 (13%) of these patients, respectively. Although patients with a diagnosis of falciparum malaria were more likely to have serious illness compared with those with vivax malaria (odds ratio [OR] = 2.9; 95% confidence interval [CI]: 2.4–3.5), this diagnosis nonetheless was associated with 32% of serious illness and 27% of fatalities. Among the seriously ill with a diagnosis of falciparum or vivax malaria, no significant difference in risk of death occurred (OR = 1.3; 95% CI: 0.7–2.5). Serious and fatal illness was predominantly anemia or altered mental state syndromes among patients with either of the species diagnoses. Plasmodium vivax was associated with a substantial share of the burden of morbidity and mortality caused by malaria in this hypo- to meso-endemic community.

Artemisinin-based combination therapies (ACTs) are the first-line treatment of uncomplicated malaria. The public health benefit and safety of repeated administration of a given ACT are poorly studied. We conducted a randomized trial comparing artemether-lumefantrine, artesunate plus amodiaquine (AS+AQ) and artesunate plus sulfadoxine-pyrimethamine (AS+SP) in patients 6 months of age and older with uncomplicated malaria in Mali from July 2005 to July 2007. The patient received the same initial treatment of each subsequent uncomplicated malaria episode except for treatment failures where quinine was used. Overall, 780 patients were included. Patients in the AS+AQ and AS+SP arms had significantly less risk of having malaria episodes; risk ratio (RR) = 0.84 (P = 0.002) and RR = 0.80 (P = 0.001), respectively. The treatment efficacy was similar and above 95% in all arms. Although all drugs were highly efficacious and well tolerated, AS+AQ and AS+SP were associated with less episodes of malaria.

Malaria rapid diagnostic tests (RDTs) could radically improve febrile illness management in remote and low-resource populations. However, reliance upon community health workers (CHWs) remains controversial because of concerns about blood safety and appropriate use of artemisinin combination therapy. This study assessed CHW ability to use RDTs safely and accurately up to 12 months post-training. We trained 65 Zambian CHWs, and then provided RDTs, job-aids, and other necessary supplies for village use. Observers assessed CHW performance at 3, 6, and 12 months post-training. Critical steps performed correctly increased from 87.5% at 3 months to 100% subsequently. However, a few CHWs incorrectly read faint positive or invalid results as negative. Although most indicators improved or remained stable over time, interpretation of faint positives fell to 76.7% correct at 12 months. We conclude that appropriately trained and supervised CHWs can use RDTs safely and accurately in community practice for up to 12 months post-training.

Antimalarials are widely used in African and Southeast Asian countries, where they are combined with other drugs for the treatment of concurrent ailments. The potential for P-glycoprotein (P-gp)-mediated drug-drug interactions (DDIs) between antimalarials and P-gp substrates was examined using a Caco-2 cell-based model. Selected antimalarials were initially screened for their interaction with P-gp based on the inhibition of rhodamine-123 (Rho-123) transport in Caco-2 cells. Verapamil (100 μM) and quinidine (1 μM) were used as positive inhibition controls. Lumefantrine, amodiaquin, and artesunate all showed blockade of Rho-123 transport. Subsequently, the inhibitory effect of these antimalarials on the bi-directional passage of digoxin (DIG) was examined. All of the drugs decreased basal-to-apical (B-A) P-gp-mediated DIG transport at concentrations of 100 μM and 1 mM. These concentrations may reflect therapeutic doses for amodiaquin and artesunate. Therefore, clinically relevant DDIs may occur between certain antimalarials and P-gp substrates in general.

Patients who recover from leishmaniasis usually show development of strong immunity and induction of interferon-γ (IFN-γ) and delayed type hypersensitivity. In a randomized trial, we analyzed the IFN-γ response by using a Quantiferon–Leishmania assay against three Leishmania peptide antigens and compared it with results of the leishmanin skin test (LST) in persons residing in areas in Iran to which zoonotic cutaneous leishmaniasis (ZCL, 181 persons), anthroponotic cutaneous leishmaniasis (ACL, 104 persons), and zoonotic visceral leishmaniasis (ZVL, 67 persons) are endemic. The percentage of persons with an IFN-γ-positive response (> 0.2 IU/mL) to three antigens and the mean concentration of IFN-γ induced by the antigens were higher for persons from areas endemic for ZVL than for persons from areas endemic for ZCL and ACL. The percentage of persons with LST-positive results (≥ 5 mm indurations) was 99%, 94%, and 70% for areas with ZCL, ACL, and ZVL, respectively. Our data indicate that the LST is significantly more sensitive than IFN-γ levels in persons who have been cured of cutaneous leishmaniasis than in persons who have been cured of ZVL.

Leishmaniasis is an emerging disease in Thailand. Herein, we report on two human immunodeficiency virus (HIV)-infected patients with leishmaniasis who presented with overlapping manifestations between cutaneous and visceral leishmaniasis. Sequencing analysis of the internal transcribed spacer 1 (ITS1) of the ribosomal RNA gene showed that the species was identical to a new species recently described in Thailand. The detection of DNA of this Leishmania species in saliva may have important implications for transmission and epidemiological studies.

The sensitivity of diagnostic methods for visceral leishmaniasis (VL) decreases because of the low number of parasites and antibody amounts in asymptomatic healthy donors who are not suitable for invasive sample acquisition procedures. Therefore, new studies are urgently needed to improve the sensitivity and specificity of the diagnostic approaches in non-invasive samples. In this study, the sensitivity of the microculture method (MCM) was compared with polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescent antibody test (IFAT) methods in an experimental murine model with asymptomatic leishmaniasis. Results showed that the percent of positive samples in ELISA, IFAT, and peripheral blood (PB) -PCR tests were 17.64%, 8.82%, and 5.88%, respectively, whereas 100% positive results were obtained with MCM and MCM-PCR methods. Thus, this study, for the first time, showed that MCM is more sensitive, specific, and economic than other methods, and the sensitivity of PCR that was performed to samples obtained from MCM was higher than sensitivity of the PCR method sampled by PB.

The glycosylphosphatidylinositol (GPI)-anchored mucins of Trypanosoma cruzi trypomastigotes play an important immunomodulatory role during the course of Chagas disease. Here, some biological activities of tGPI-mucins from four T. cruzi isolates, including benznidazole-susceptible (BZS-Y), benznidazole-resistant (BZR-Y), CL, and Colombiana, were evaluated. GPI-mucins were able to differentially trigger the production of interleukin-12 and nitric oxide in BALB/c macrophages and modulate LLC-MK2 cell invasion. The significance of these variations was assessed after analysis of the terminal α-galactosyl residues. Enzymatic treatment with α-galactosidase indicated a differential expression of O-linked α-galactosyl residues among the strains, with higher expression of this sugar in BZS-Y and BZR-Y T. cruzi populations followed by Colombiana and CL. Unweighted pair group method analysis of the carbohydrate anchor profile and biological parameters allowed the clustering of two groups. One group includes Y and CL strains (T. cruzi II and VI), and the other group is represented by Colombiana strain (T. cruzi I).

The seroprevalence of Entamoeba histolytica infection in the residents of seven provinces in China was examined by using an enzyme-linked immunosorbent assay with a crude antigen and a recombinant surface antigen, C-Igl, of the parasites. A total of 1,312 serum samples were investigated. The positivity rates for these two antigens were 11.05% and 6.25%, respectively. There was no significant difference in the seropositivity to E. histolytica between men and women. We used a logistic regression model and maximal-likelihood methods to estimate the prevalence of E. histolytica infection from sequential serologic data. Seropositivity in Sichuan, Guizhou, and Sinkiang Provinces was higher than that in Beijing, Shanghai, and Qinghai Provinces. The present study provides an overview of seropositivity to E. histolytica infection in seven provinces in China and use the logistic regression model estimation method to achieve a more accurate measure of amebiasis incidence.

We investigated serum total immunoglobulin E (IgE), IgG, and IgG1 levels in patients with and without echinococcosis-induced anaphylactic shock. This was a case-control study of 11 patients with echinococcosis-induced anaphylactic shock and 22 echinococcosis patients with cyst rupture but without anaphylactic shock. Blood was collected before surgery (T0), at the time of cyst rupture (T1), and shock (Tx), 1 h (T2), 1 day (T3), and 1 week (T4) after cyst rupture. Serum IgE, IgG, and IgG1 were determined by enzyme-linked immunosorbent assay. Serum IgE, IgG, and IgG1 levels were significantly higher in patients who developed anaphylactic shock at all time points. Increased pre-surgical IgG and IgG1 levels were identified to be a significant risk factors for developing anaphylactic shock. The results showed that a serum IgG concentration of 312.25 μg/mL could be used as a cut-off point to predict whether an echinococcosis patient would develop anaphylactic shock.

Triatoma infestans and Panstrongylus megistus are relevant Chagas disease vectors. An apparent segregation among these triatomine species inside human households was suggested to rely on mutual repellence between them. However, P. megistus and T. infestans show aggregation responses to chemical signals emitted by the other species. These findings do not rule out the possibility that stimuli other than chemical signals could mediate repellence when these species exploit shelters simultaneously. In the present study, we investigated how P. megistus and T. infestans exploit shelters in controlled laboratory conditions and how insect density and environmental illumination modulate this behavior. We evaluated whether these species aggregate inside shelters or mutually repel each other. Panstrongylus megistus and T. infestans show specific patterns of shelter exploitation, which are differentially affected by insect density and environment illumination. In particular, P. megistus is more sensitive to insect density than T. infestans, whereas T. infestans shows higher sensitivity to illumination than P. megistus. Nevertheless, these species exploit shelters randomly without any apparent repellence.

Indoor residual spraying (IRS) has become an increasingly popular method of insecticide use for malaria control, and many recent studies have reported on its effectiveness in reducing malaria burden in a single community or region. There is a need for systematic review and integration of the published literature on IRS and the contextual determining factors of its success in controlling malaria. This study reports the findings of a meta-regression analysis based on 13 published studies, which were chosen from more than 400 articles through a systematic search and selection process. The summary relative risk for reducing malaria prevalence was 0.38 (95% confidence interval = 0.31–0.46), which indicated a risk reduction of 62%. However, an excessive degree of heterogeneity was found between the studies. The meta-regression analysis indicates that IRS is more effective with high initial prevalence, multiple rounds of spraying, use of DDT, and in regions with a combination of Plasmodium falciparum and P. vivax malaria.