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Background: Helicobacter pylori coinfection in human immunodeficiency virus (HIV) patients has been associated with higher CD4+ cell counts and lower HIV-1 viral loads, with the underlying mechanisms being unknown. The objective of this study was to investigate the impact of H. pylori infection on markers of T-cell activation in HIV-positive and HIV-negative individuals., Methods: In a cross-sectional, observational study, HIV patients (n = 457) and HIV-negative blood donors (n = 79) presenting to an HIV clinic in Ghana were enrolled. Data on clinical and sociodemographic parameters, CD4+/CD8+ T-cell counts, and HIV-1 viral load were recorded. Helicobacter pylori status was tested using a stool antigen test. Cell surface and intracellular markers related to T-cell immune activation and turnover were quantified by flow cytometry and compared according to HIV and H. pylori status., Results: Helicobacter pylori infection was associated with decreased markers of CD4+ T-cell activation (HLA-DR+CD38+CD4+; 22.55% vs 32.70%; P = .002), cell proliferation (Ki67; 15.10% vs 26.80%; P = .016), and immune exhaustion (PD-1; 32.45% vs 40.00%; P = .005) in 243 antiretroviral therapy (ART)-naive patients, but not in 214 patients on ART. In HIV-negative individuals, H. pylori infection was associated with decreased frequencies of activated CD4+ and CD8+ T cells (6.31% vs 10.40%; P = .014 and 18.70% vs 34.85%, P = .006, respectively)., Conclusions: Our findings suggest that H. pylori coinfection effectuates a systemic immune modulatory effect with decreased T-cell activation in HIV-positive, ART-naive patients but also in HIV-negative individuals. This finding might, in part, explain the observed association of H. pylori infection with favorable parameters of HIV disease progression., Clinical Trials Registration: Clinicaltrials.gov NCT01897909., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: The current Japanese encephalitis (JE) vaccination regimen requires two doses and 4 weeks to complete, which may not always be feasible for travelers on short notice. One of the primary endpoints of this phase III study was to demonstrate noninferiority of immune responses to a JE vaccine following an accelerated 1-week JE vaccination regimen administered concomitantly with a rabies vaccine as compared to a standard 4-week JE regimen alone. In addition, the immunogenicity of concomitant administration of JE and rabies vaccines following standard regimens was evaluated, as well as the tolerability and safety profile of each regimen under study., Methods: Healthy adults aged 18 to ≤65 years were randomized to regimens with an accelerated or standard schedule: JE+rabies-standard (n = 167), JE+rabies-accelerated (n = 217) or JE-standard (n = 56). Immunogenicity against JE antigen was assessed by a 50% plaque reduction neutralization test (PRNT50 ) titer of ≥1 : 10, measured 28 days after last active vaccine (LAV) administration. Solicited reactions were collected 7 days after each vaccination; spontaneously reported adverse events (AEs) and serious AEs were monitored up to day 57. This paper reports results until day 57., Results: Noninferiority of immune responses was established for JE+rabies-accelerated compared to the JE-standard regimen 28 days after LAV administration. Overall, 99% and 100% of subjects in the JE+rabies-accelerated and JE-standard groups, respectively, achieved PRNT50 titers of ≥1 : 10 at 28 days after LAV administration. No impact of concomitant rabies vaccination was observed either on immune responses or on the safety profile of the JE vaccine., Conclusions: This was the first randomized, controlled trial that demonstrated the strong short-term immunogenicity of a new, accelerated, 1-week JE-regimen, which was noninferior to that of the standard regimen, with a satisfactory tolerability and safety profile and no impact of concomitant rabies vaccination. This accelerated regimen, if licensed, could potentially be a valid alternative for individuals requiring a primary series of JE vaccination and rabies pre-exposure prophylaxis on short notice., (© 2015 International Society of Travel Medicine.)

Objectives: The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon., Methods: In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (≥1000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls., Results: At Month 12, 38/238 (16%) patients experienced virological failure (≥1000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n = 18) and K103N (n = 10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P = 0.77). Lower CD4 count at baseline (OR per 100 cells/mm(3) lower 1.41, 95% CI 1.02-1.96, P = 0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P < 0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence., Conclusions: Virological failure after 1 year of ART was not associated with minority drug resistance at baseline but with incomplete adherence. Strategies to assure adherence and uninterrupted drug supplies are pivotal factors for therapy success., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Parenteral artesunate is recommended as first-line therapy for severe malaria. While its efficacy is firmly established, data on safety are still incomplete. Delayed hemolysis has been described in hyperparasitemic nonimmune travelers, but it is unknown if African children are equally at risk., Methods: Children aged 6 to 120 months with severe malaria were followed up after treatment with parenteral artesunate in Lambaréné, Gabon, and Kumasi, Ghana. The primary outcome was incidence of delayed hemolysis on day 14., Results: In total, 72 children contributed complete data sets necessary for primary outcome assessment. Delayed hemolysis was detected in 5 children (7%), with 1 child reaching a nadir in hemoglobin of 2.8 g/dL. Patients with delayed hemolysis had higher parasite counts on admission (geometric mean parasite densities (GMPD) 306 968/µL vs 92 642/µL, P = .028) and were younger (median age: 24 months vs 43 months, P = .046) than the rest of the cohort. No correlation with sickle cell trait or glucose-6-phosphate-dehydrogenase deficiency was observed., Conclusions: Delayed hemolysis is a frequent and relevant complication in hyperparasitemic African children treated with parenteral artesunate for severe malaria. Physicians should be aware of this complication and consider prolonged follow-up., Clinical Trials Registration: Pan-African Clinical Trials Registry: PACTR201102000277177 (www.pactr.org)., (© The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Ciguatera fish poisoning is a travel-related illness characterized by a combination of gastrointestinal and neurological symptoms in persons who eat ciguatoxic seafood in endemic areas., Methods: In 2009, an outbreak of the disease on a refrigerator vessel in the port of Hamburg was investigated. The ship's crew fell ill after they ate fish from a catch in the Caribbean 2 weeks earlier. All 15 sailors on board were examined by port medical officers. Samples of blood and stool specimens were taken from symptomatic sailors. The frozen fish was secured for the prevention of further disease spreading and additional diagnostic tests., Results: All but one sailor ate the fish. The intoxication resulted in gastrointestinal or neurological symptoms in all 14 sailors who consumed the fish and persisted in varying degrees in 93% of sailors over at least 14 days. No fatality occurred, but two seamen were "unfit for duty" on the ship due to severity of symptoms. The diagnosis was supported by the fact that all seafarers who consumed the same reef fish, experienced typical signs, symptoms, and time course consistent with ciguatera fish poisoning. The fish from the catch in the Caribbean was identified as Caranx sexfasciatus (Bigeye Trevally) and Cephalopholis miniata (Red Grouper). An experimental assay later confirmed presence of the ciguatoxin in the fish., Conclusions: Sailors are an occupational group at risk for ciguatera fish poisoning due to potentially unsafe food sources during international travel. Even if no fatality occurred, the disease affected marine operations due to high attack rates and chronicity of symptoms. Medical doctors must be aware that ciguatera fish poisoning is a risk for seafarers traveling in tropical and subtropical areas. Stocking of food in affected ports from safe sources, adequate training of ship cooks, and informing sailors about the risk of fishing are needed to prevent disease occurrence in seafarers in international trade and traffic., (© 2012 International Society of Travel Medicine.)

A needlestick injury occurred during an animal experiment in the biosafety level 4 laboratory in Hamburg, Germany, in March 2009. The syringe contained Zaire ebolavirus (ZEBOV) mixed with Freund's adjuvant. Neither an approved treatment nor a postexposure prophylaxis (PEP) exists for Ebola hemorrhagic fever. Following a risk-benefit assessment, it was recommended the exposed person take an experimental vaccine that had shown PEP efficacy in ZEBOV-infected nonhuman primates (NHPs) [12]. The vaccine, which had not been used previously in humans, was a live-attenuated recombinant vesicular stomatitis virus (recVSV) expressing the glycoprotein of ZEBOV. A single dose of 5 × 10(7) plaque-forming units was injected 48 hours after the accident. The vaccinee developed fever 12 hours later and recVSV viremia was detectable by polymerase chain reaction (PCR) for 2 days. Otherwise, the person remained healthy, and ZEBOV RNA, except for the glycoprotein gene expressed in the vaccine, was never detected in serum and peripheral blood mononuclear cells during the 3-week observation period.

Background: An outbreak of chikungunya virus infection emerged in the southwest Indian Ocean islands in 2005, spread out to India, and resulted in an ongoing outbreak that has involved >1.5 million patients, including travelers who have visited these areas., Methods: Our study investigated 69 travelers who developed signs and symptoms compatible with chikungunya fever after returning home from countries involved in the epidemic. Twenty cases of infection that were confirmed by serological analysis, polymerase chain reaction, and/or cell culture were investigated., Results: All patients experienced flulike symptoms with fever and joint pain. No serious complications were observed, but 69% of the patients had persistent arthralgia for >2 months, and 13% had it for >6 months. Viral RNA could be detected in blood samples using reverse-transcriptase polymerase chain reaction in 4 of 4 patients who presented to a health care facility during their first week of illness, and the virus was successfully isolated from blood samples obtained from 2 of these patients. Chikungunya virus-specific immunoglobulin M and/or immunoglobulin G antibodies were detected in all patients. However, initial testing of serum samples yielded negative results for 3 of 5 patients during the first week., Conclusions: Chikungunya fever must be considered in travelers who develop fever and arthritis after traveling to areas affected by an ongoing epidemic. Related arthritis mainly affects smaller joints and often persists for extended periods. Serological testing may have negative results during the first week of the disease; diagnosis using polymerase chain reaction appears to be more reliable during this time. Travelers to areas of epidemicity should be informed of the risk of infection and of adequate preventive measures, such as protection against mosquitos.

Background: Malaria, anemia, and malnutrition contribute substantially to childhood morbidity in sub-Saharan Africa, but their respective roles and interactions in conferring disease are complex. We aimed to investigate these interactions., Methods: In 2002, we assessed plasmodial infection, anemia, and nutritional indices in 2 representative surveys comprising >4000 children in northern Ghana., Results: Infection with Plasmodium species was observed in 82% and 75% of children in the rainy and dry season, respectively. The fraction of fever attributable to malaria was 77% in the rainy season and 48% in the dry season and peaked in children of rural residence. Anemia (hemoglobin level, <11 g/dL) was seen in 64% of children and was, in multivariate analysis, associated with young age, season, residence, parasitemia, P. malariae coinfection, and malnutrition (odds ratio [OR], 1.68 [95% confidence interval [CI], 1.38-2.04]). In addition, malnutrition was independently associated with fever (axillary temperature, > or = 37.5 degrees C; OR, 1.59 [95% CI, 1.13-2.23]) and clinical malaria (OR, 1.67 [95% CI, 1.10-2.50])., Conclusions: Malnutrition is a fundamental factor contributing to malaria-associated morbidity and anemia, even if the latter exhibits multifactorial patterns. Our data demonstrate that malaria-control programs alone may not have the desired impact on childhood morbidity on a large scale without concomitant nutrition programs.

In areas endemic for onchocerciasis, a small number of individuals show no detectable infection with Onchocerca volvulus despite an apparently similar exposure to the transmitting blackflies. Such individuals have been termed putatively immune. Since several studies have indicated marked host differences in attractiveness for blood-seeking insects, putative immunity in O. volvulus infection may result, at least in part, from low vector attractiveness of the respective individuals. In an area hyperendemic for onchocerciasis (Guinea), where Simulium yahense is the predominant vector, we organized fly catches by putatively immune individuals and individuals with moderate-to-high worm counts. No differences were found between the 2 groups with respect to (i) the attraction of blackflies, (ii) the attraction of blackflies infected with O. volvulus, or (iii) the numbers of O. volvulus larvae carried by the attracted blackflies.

Although considered of critical importance, the mode of helper T-lymphocyte function in Onchocerca volvulus infection is still unclear including the role of the Th1/Th2 dichotomy. We studied the delayed-type hypersensitivity (DTH) reaction, which is the classical Th1 response, to O. volvulus antigens in Africans exposed and not exposed to the infection. DTH reactions were found in a small percentage of patients with generalized onchocerciasis, but in a high percentage of patients with localized onchocerciasis, in putatively immune subjects, and also in non-exposed individuals, which may be due to cross-reactivity with other nematodes. These findings support the notions of (i) prenatal influence of maternal O. volvulus infection preventing development of Th1 responses and/or (ii) suppression of Th1 responses by the infection itself.

Intrasplenic lesions can cause diagnostic difficulties because malignant diseases can be excluded only by histologic examination. We present the cases of two patients with splenic manifestations of loiasis. Both patients had visited central Africa. Several years later, intrasplenic lesions were found during routine examinations (for chest trauma and employment, respectively). Both patients underwent splenectomies because malignant lymphoma was suspected. In both cases, histologic examination of the spleen showed eosinophilic granulomata with multiple Loa loa microfilariae.

The effectiveness of mebendazole as a microfilaricide in patients with loiasis was studied. The drug regimen was 1 g twice daily for 21 days in adults. During and after treatment, the microfilarial density was unchanged. Therefore, mebendazole has no direct effect on the microfilarial density of Loa loa.

Most commonly used antiamoebic drugs are effective in invasive amebiasis, but their response against trophozoites of Entamoeba histolytica, present in the lumen of the human colon, is inadequate. We report the development of an antiamoebic drug carrier that may be effective against luminal infections. Our preparation consists of small silica particles (5-10 microns in diameter) covalently linked to a potent antiamoebic drug, 2-(4-aminophenoxymethyl)-5-nitro-1-methyl imidazole. Silica-drug particles were injected into mice, hamsters, and guinea pigs. We found that trophozoites phagocytosed the particles in vivo and in vitro, followed by rapid cell death due to the released drug. Analysis of mouse serum revealed that no drug was absorbed from the intestine after placement of the drug-containing particles in the intestine. The antiamoebic activity of particles recovered from the intestine was almost fully retained. This novel antiamoebic concept may be useful for luminal therapy for asymptomatic amebiasis and may minimize side effects and frequency of administration.