Viravarn Luvira

Management of Strongyloides stercoralis: a puzzling parasite

Strongyloides stercoralis is one of the common parasites in tropical areas. It can result in severe clinical syndromes, hyperinfection syndrome or disseminated strongyloidiasis in immunocompromised patients. The treatment of strongyloidiasis is a challenge for clinicians in clinical practice. Failure of treatment is due to autoinfection caused by the parasite life cycle and impairment of host immunity. Ivermectin currently is the treatment of choice. When compared with thiabendazole, it has shown a similar efficacy with better tolerability. However, there is neither consensus in duration of treatment nor in repetition of doses. The keys for management of this tough parasite include proper evaluation and prevention. Stool examination with high sensitivity techniques such as Baermann technique, filter-paper culture and agar-plate culture and specific IgG serology should be used in evaluation for 1 to 2 years. Screening, both stool examination and serology, before patients have immunosuppressive treatment is needed to prevent the severe form of strongyloidiasis.

Comparative Diagnosis of Strongyloidiasis in Immunocompromised Patients.

Strongyloides hyperinfection syndrome and disseminated strongyloidiasis frequently occur in immunocompromised persons and can lead to high complication and mortality rates. Thus, detection of Strongyloides stercolaris in those patients is crucial. The present study aimed to determine the prevalence of strongyloidiasis and compare the detection rates of different strongyloidiasis detection methods. We conducted a cross-sectional study of 135 adults with various immunocompromising conditions (corticosteroid usage, chemotherapy, hematologic malignancies, organ transplants, use of immunosuppressive agents, and symptomatic human immunodeficiency virus infection) in Phramongkutklao Hospital, Bangkok, Thailand. All patients were asked to undergo serology testing for Strongyloides IgG by indirect enzyme-linked immunosorbent assay (ELISA), and 3 days of stool collection for use in a simple smear along with formalin-ether concentration and agar plate techniques. Prevalence rates of strongyloidiasis were 5% by stool concentration technique, 5.4% by IgG-ELISA, and 6.7% by agar plate culture. Three of the eight strongyloidiasis cases in this study had hyperinfection syndrome. The tested risk factors of age, sex, occupation, and immunocompromising condition were not associated with Strongyloides infestation. Serology was only 42.9% sensitive (positive predictive value), but it was 96.3% specific (negative predictive value). In conclusion, prevalence rates of strongyloidiasis in this study were 5-7%. Although agar plate culture was the most sensitive technique, the other diagnostic methods might be alternatively used.

Safety and immunogenicity of a live attenuated influenza H5 candidate vaccine strain A/17/turkey/Turkey/05/133 H5N2 and its priming effects for potential pre-pandemic use: a randomised, double-blind, placebo-controlled trial

Summary Background The emergence of highly pathogenic avian influenza H5N1 viruses has raised concerns about their pandemic potential. Vaccination is the most effective way of preventing influenza. In this study, we investigated the safety and immunogenicity of an avian H5N2 live attenuated influenza vaccine (LAIV H5N2) in healthy Thai adults and its priming immune responses with an H5N1 inactivated vaccine boost. Methods This study was done at the Vaccine Trial Centre at Mahidol University, Bangkok, Thailand and was divided into two parts. Part 1 consisted of a randomised, double-blind, placebo-controlled trial done over 18 months. We randomly assigned (2:1) healthy Thai adults aged 18–49 years with a computer generated randomisation sequence (blocks of six) to receive either two intranasal doses (0·25 mL per nostril) of LAIV H5N2 (101 participants) or placebo (51 participants) 21 days apart. For part 2, an open-label trial was done in which previously vaccinated participants (40 from LAIV H5N2 group and 20 placebo) were given one intramuscular dose (0·5 mL) of H5N1 booster vaccine. Participants, investigators, and site-study workers were blinded from randomisation. Immune responses after subsequent immunisation were evaluated using haemagglutination-inhibition and microneutralisation assays and circulating follicular T-helper cells and plasmablast cells were measured in serum and whole blood. The trials are registered with ClinicalTrials.gov, numbers NCT01841918 and NCT02229357. Findings Between Feb 4, 2013, and Feb 28, 2013, 256 individuals were screened, of whom 152 participants were enrolled in part 1 of this study. LAIV H5N2 vaccine was well tolerated. Viral shedding was detected in only six (6%) of 101 participants in the vaccine group 1 day after the first vaccination and in and two (2%) of 98 participants in the group after the second vaccination. There was no serious adverse event in both groups. 51 (50%) of 101 participants in the vaccine group and 28 (55%) of 51 in the placebo group reported at least one adverse event. 80 (84%) of 95 events in the vaccine group and 32 (78%) of 43 events in the placebo groups were reportedly suspected adverse events, probably related to the vaccine; however, most were mild in nature. After two doses of vaccine, 13 (13%) of 100 participants in the vaccine group had an increase in haemagglutination-inhibition titre of more than four-fold and four (4%) of 100 vaccinees developed a rise in neutralisng antibody titre of more than four-fold. 1 year later, after a booster with an inactivated H5N1 vaccine (part 2), 39 (98%) of 40 participants who had previously been vaccinated with LAIV H5N2 had an increase in haemagglutination-inhibition titre of greater than four-fold as early as day 7 compared with three (15%) of 20 participants in the placebo group. Peak geometric mean titre (GMT) for haemagglutination-inhibition antibodies in the previously LAIV H5N2 vaccinated group (566·89 [95% CI 436·97–735·44]) were significantly higher than among those who previously received placebo (25·49 [11·82–54·96]; p<0·0001). The peak GMT by neutralising antibody assay in the H5N2 vaccinated group (1395·85 [1040·79–1872·03]) was also significantly higher than that observed in the placebo group (17·41 [9·05–33·48]; p<0·0001). Importantly, higher cross-reactive haemagglutination-inhibition antibody titres against H5N1 (clades 1, 2.1.3.2, and 2.3.4) were detected in the LAIV H5N2 experienced group than the naive group (p<0·0001). Interpretation Our data suggest that LAIV vaccination induces long-lasting memory immune responses. The limitation of this study was that part 2 was designed as a proof-of-concept study by contrast with part 1. Funding WHO.

Clinical Trial of an Oral Live Shigella sonnei Vaccine Candidate, WRSS1, in Thai Adults

ABSTRACT Live attenuated Shigella sonnei vaccine candidate WRSS1, previously tested in U.S. and Israeli volunteers, was evaluated in a population of adult Thai volunteers in which the organism is endemic. In a randomized placebo-controlled, double-blind design, inpatient participants received a single oral dose of 1.6 × 104 CFU of WRSS1. The vaccine was generally well tolerated, with equal numbers of vaccinees and placebo controls showing mild symptoms. Only 3 of 13 vaccinees (23%) had culture-positive stools, while a total of 9 vaccinees were positive by PCR. Lack of vaccine shedding in volunteers correlated with lack of clinical symptoms and immune responses, just as the duration of fecal shedding correlated directly with stronger immune responses. Two months following immunization, 10 vaccinees and 10 newly recruited naive controls received a challenge dose of 1,670 CFU of virulent S. sonnei strain 53G. This dose had previously demonstrated a 75% attack rate for dysentery in Thai volunteers. However, in this study the attack rate for dysentery in naive controls after challenge was 20%. Based on clinical record summaries, 3 vaccinees and 5 naive controls experienced clinically relevant illness (diarrhea/dysentery/fever/shigellosis), and a 40% vaccine efficacy was calculated. When these data are compared to those for the performance of this vaccine candidate in more naive populations, it is clear that a single oral dose of WRSS1 at 104 CFU failed to achieve its full potential in a population in which the organism is endemic. Higher doses and/or repeated immunizations may contribute to improved vaccine shedding and consequent elevation of protective immune responses in a population in which the organism is endemic. (The study has been registered at ClinicalTrials.gov under registration no. NCT01080716.)

Delayed care-seeking and outcome of dengue-infected patients

A retrospective cohort study was conducted to assess the effect of early (1–4 days after fever onset) and delayed (≥5 days) care-seeking on outcomes of dengue-infected patients. We used data of adult dengue-infected patients treated in Bangkok, Thailand between June 2012 and September 2013. There were 110 patients in the early care-seeking group and 100 in the delayed care-seeking group. There were no deaths. Bleeding complications were not significantly different between the two groups while the latter group had a significantly higher rate of admission compared with the former (98% versus 91.8%, respectively; P = 0.04). Being female was the only factor significantly associated with delayed care-seeking (63.0% versus 45.5%; P = 0.01).

Accuracy of dengue clinical diagnosis with and without NS1 antigen rapid test: Comparison between human and Bayesian network model decision

Differentiating dengue patients from other acute febrile illness patients is a great challenge among physicians. Several dengue diagnosis methods are recommended by WHO. The application of specific laboratory tests is still limited due to high cost, lack of equipment, and uncertain validity. Therefore, clinical diagnosis remains a common practice especially in resource limited settings. Bayesian networks have been shown to be a useful tool for diagnostic decision support. This study aimed to construct Bayesian network models using basic demographic, clinical, and laboratory profiles of acute febrile illness patients to diagnose dengue. Data of 397 acute undifferentiated febrile illness patients who visited the fever clinic of the Bangkok Hospital for Tropical Diseases, Thailand, were used for model construction and validation. The two best final models were selected: one with and one without NS1 rapid test result. The diagnostic accuracy of the models was compared with that of physicians on the same set of patients. The Bayesian network models provided good diagnostic accuracy of dengue infection, with ROC AUC of 0.80 and 0.75 for models with and without NS1 rapid test result, respectively. The models had approximately 80% specificity and 70% sensitivity, similar to the diagnostic accuracy of the hospital’s fellows in infectious disease. Including information on NS1 rapid test improved the specificity, but reduced the sensitivity, both in model and physician diagnoses. The Bayesian network model developed in this study could be useful to assist physicians in diagnosing dengue, particularly in regions where experienced physicians and laboratory confirmation tests are limited.