Heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination against SARS-CoV-2 infection: 1-year follow-up of a phase 1/2 open-label trial.

BACKGROUND: Inactivated whole-virus vaccination elicits immune responses to both SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, like natural infections. A heterologous Ad26.COV2.S booster given at two different intervals after primary BBIBP-CorV vaccination was safe and immunogenic at days 28 and 84, with higher immune responses observed after the longer pre-boost interval. We describe booster-specific and hybrid immune responses over 1 year. METHODS: This open-label phase 1/2 study was conducted in healthy Thai adults aged ≥ 18 years who had completed primary BBIBP-CorV primary vaccination between 90-240 (Arm A1; n = 361) or 45-75 days (Arm A2; n = 104) before enrolment. All received an Ad26.COV2.S booster. We measured anti-S and anti-N IgG antibodies by Elecsys®, neutralizing antibodies by SARS-CoV-2 pseudovirus neutralization assay, and T-cell responses by quantitative interferon (IFN)-γ release assay. Immune responses were evaluated in the baseline-seronegative population (pre-booster anti-N < 1.4 U/mL; n = 241) that included the booster-effect subgroup (anti-N < 1.4 U/mL at each visit) and the hybrid-immunity subgroup (anti-N ≥ 1.4 U/mL and/or SARS-CoV-2 infection, irrespective of receiving non-study COVID-19 boosters). RESULTS: In Arm A1 of the booster-effect subgroup, anti-S GMCs were 131-fold higher than baseline at day 336; neutralizing responses against ancestral SARS-CoV-2 were 5-fold higher than baseline at day 168; 4-fold against Omicron BA.2 at day 84. IFN-γ remained approximately 4-fold higher than baseline at days 168 and 336 in 18-59-year-olds. Booster-specific responses trended lower in Arm A2. In the hybrid-immunity subgroup at day 336, anti-S GMCs in A1 were 517-fold higher than baseline; neutralizing responses against ancestral SARS-CoV-2 and Omicron BA.2 were 28- and 31-fold higher, respectively, and IFN-γ was approximately 14-fold higher in 18-59-year-olds at day 336. Durable immune responses trended lower in ≥ 60-year-olds. CONCLUSION: A heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination induced booster-specific immune responses detectable up to 1 year that were higher in participants with hybrid immunity. CLINICAL TRIALS REGISTRATION: NCT05109559.

Single Ad26.COV2.S booster dose following two doses of BBIBP-CorV vaccine against SARS-CoV-2 infection in adults: Day 28 results of a phase 1/2 open-label trial.

BACKGROUND: The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.COV2.S booster dose given at different intervals after 2 doses of BBIBP-CorV are presented. METHODS: This open-label phase 1/2 trial was conducted in healthy adults in Thailand who had completed 2-dose primary vaccination with BBIBP-CorV. Participants received a single booster dose of Ad26.COV2.S (5 × 1010 virus particles) 90-240 days (Group A1; n = 360) or 45-75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Safety and immunogenicity were assessed over 28 days. Binding IgG antibodies to the full-length pre-fusion Spike and anti-nucleocapsid proteins of SARS-CoV-2 were measured by enzyme-linked immunosorbent assay. The SARS-CoV-2 pseudovirus neutralization assay and live virus microneutralization assay were used to quantify the neutralizing activity of antibodies against ancestral SARS-CoV-2 (Wuhan-Hu-1) and the delta (B.1.617.2) and omicron (B.1.1.529/BA.1 and BA.2) variants. The cell-mediated immune response was measured using a quantitative interferon (IFN)-γ release assay in whole blood. RESULTS: Solicited local and systemic adverse events (AEs) on days 0-7 were mostly mild, as were unsolicited vaccine-related AEs during days 0-28, with no serious AEs. On day 28, anti-Spike binding antibodies increased from baseline by 487- and 146-fold in Groups A1 and A2, and neutralizing antibodies against ancestral SARS-CoV-2 by 55- and 37-fold, respectively. Humoral responses were strongest against ancestral SARS-CoV-2, followed by the delta, then the omicron BA.2 and BA.1 variants. T-cell-produced interferon-γ increased approximately 10-fold in both groups. CONCLUSIONS: A single heterologous Ad26.COV2.S booster dose after two BBIBP-CorV doses was well tolerated and induced robust humoral and cell-mediated immune responses measured at day 28 in both interval groups. CLINICAL TRIALS REGISTRATION: NCT05109559.

PCR Diagnosis of Opisthorchis viverrini and Haplorchis taichui Infections in a Lao Community in an area of endemicity and comparison of diagnostic methods for parasitological field surveys.

Opisthorchiasis is a major public health problem in Southeast Asia. Affected individuals often have mixed infections with the liver fluke Opisthorchis viverrini and minute intestinal flukes such as Haplorchis taichui. The usual methods of diagnosing these infections involve the demonstration of fluke eggs in stool samples under light microscopy, but sensitivity and specificity are low. We developed two PCR tests that detect and discriminate between O. viverrini and H. taichui infections. PCR tests were validated by stool samples from purged individuals. We then applied the PCR tests to estimate the prevalence of O. viverrini and H. taichui infections from a random sample of individuals selected from a community in an area of endemicity in Khong District, Laos. PCR results were compared with those from the Kato-Katz (KK) method and the formalin-ether concentration technique (FECT). When validated with purge results, PCR tests of O. viverrini and H. taichui had sensitivities of 93.7% (95% confidence interval [CI], 85.8 to 97.9%) and 73.3% (95% CI, 60.3 to 83.9%) and could detect as little as 0.75 pg DNA and 1.32 ng DNA, respectively. The PCR-determined community prevalences of O. viverrini and H. taichui infections were 63.9% (95% CI, 54.1 to 72.9%) and 30.6% (95% CI, 22.1 to 40.2%), respectively. Using PCR as the gold standard to detect O. viverrini, three KK thick smears performed comparably well, whereas one KK smear and FECT were poorer (sensitivities of 91.4% [95% CI, 81.0 to 97.1%,], 62.3% [95% CI, 49.8 to 73.7%], and 49.3% [95% CI, 37.0 to 61.6%], respectively). PCR may be a valuable and sensitive diagnostic tool, particularly for low-intensity O. viverrini and H. taichui infections.

Influenza vaccination in pregnancy: current evidence and selected national policies.

In several countries, pregnant women are recommended seasonal influenza vaccination and identified as a priority group for vaccination in the event of a pandemic. We review the evidence for the risks of influenza and the risks and benefits of seasonal influenza vaccination in pregnancy. Data on influenza vaccine safety in pregnancy are inadequate, but the few published studies report no serious side-effects in women or their infants, including no indication of harm from vaccination in the first trimester. National policies differ widely, mainly because of the limited data available, particularly on vaccination in the first trimester. The evidence of excess morbidity during seasonal influenza supports vaccinating healthy pregnant women in the second or third trimester and those with comorbidities in any trimester. The evidence of excess mortality in two previous influenza pandemics supports vaccinating in any trimester during a pandemic.

Harnessing the wealth of Chinese scientific literature: schistosomiasis research and control in China.

The economy of China continues to boom and so have its biomedical research and related publishing activities. Several so-called neglected tropical diseases that are most common in the developing world are still rampant or even emerging in some parts of China. The purpose of this article is to document the significant research potential from the Chinese biomedical bibliographic databases. The research contributions from China in the epidemiology and control of schistosomiasis provide an excellent illustration. We searched two widely used databases, namely China National Knowledge Infrastructure (CNKI) and VIP Information (VIP). Employing the keyword "Schistosoma" and covering the period 1990-2006, we obtained 10,244 hits in the CNKI database and 5,975 in VIP. We examined 10 Chinese biomedical journals that published the highest number of original research articles on schistosomiasis for issues including languages and open access. Although most of the journals are published in Chinese, English abstracts are usually available. Open access to full articles was available in China Tropical Medicine in 2005/2006 and is granted by the Chinese Journal of Parasitology and Parasitic Diseases since 2003; none of the other journals examined offered open access. We reviewed (i) the discovery and development of antischistosomal drugs, (ii) the progress made with molluscicides and (iii) environmental management for schistosomiasis control in China over the past 20 years. In conclusion, significant research is published in the Chinese literature, which is relevant for local control measures and global scientific knowledge. Open access should be encouraged and language barriers removed so the wealth of Chinese research can be more fully appreciated by the scientific community.

Prevention and control of dengue-the light at the end of the tunnel.

Advances in the development of new dengue control tools, including vaccines and vector control, herald a new era of desperately needed dengue prevention and control. The burden of dengue has expanded for decades, and now affects more than 120 countries. Complex, large-scale global forces have and will continue to contribute to the expansion of dengue, including population growth, unplanned urbanisation, and suboptimal mosquito control in urban centres. Although no so-called magic bullets are available, there is new optimism following the first licensure of a dengue vaccine and other promising vaccine candidates, and the development of novel vector control interventions to help control dengue and other expanding mosquito-borne diseases such as Zika virus. Implementation of effective and sustainable immunisation programmes to complement existing methods will add complexity to the health systems of affected countries, which have varying levels of robustness and maturity. Long-term high prioritisation and adequate resources are needed. The way forward is full commitment to addressing a complex disease with a set of solutions integrating vaccination and vector control methods. A whole systems approach is thus needed to integrate these various approaches and strategies for controlling dengue within the goal of universal health coverage. The ultimate objective of these interventions will be to reduce the disease burden in a sustainable and equitable manner.

Efficacy of praziquantel against Schistosoma mekongi and Opisthorchis viverrini: a randomized, single-blinded dose-comparison trial.

BACKGROUND: Schistosomiasis and opisthorchiasis are of public health importance in Southeast Asia. Praziquantel (PZQ) is the drug of choice for morbidity control but few dose comparisons have been made. METHODOLOGY: Ninety-three schoolchildren were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of infections were determined by a rigorous diagnostic effort (3 stool specimens, each examined with triplicate Kato-Katz) before and 28-30 days after treatment. Ninety children with full baseline data were randomized to receive PZQ: the 40 mg/kg standard single dose (n = 45) or a 75 mg/kg total dose (50 mg/kg+25 mg/kg, 4 hours apart; n = 45). Adverse events were assessed at 3 and 24 hours posttreatment. PRINCIPAL FINDINGS: Baseline infection prevalence of S. mekongi and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were 75.0% (95% confidence interval (CI): 56.6-88.5%) and 80.8% (95% CI: 60.6-93.4%) for 40 mg/kg and 75 mg/kg PZQ, respectively (P = 0.60). O. viverrini cure rates were significantly different at 71.4% (95% CI: 53.4-84.4%) and 96.6% (95% CI: not defined), respectively (P = 0.009). Egg reduction rates (ERRs) against O. viverrini were very high for both doses (>99%), but slightly lower for S. mekongi at 40 mg/kg (96.4% vs. 98.1%) and not influenced by increasing diagnostic effort. O. viverrini cure rates would have been overestimated and no statistical difference between doses found if efficacy was based on a minimum sampling effort (single Kato-Katz before and after treatment). Adverse events were common (96%), mainly mild with no significant differences between the two treatment groups. CONCLUSIONS/SIGNIFICANCE: Cure rate from the 75 mg/kg PZQ dose was more efficacious than 40 mg/kg against O. viverrini but not against S. mekongi infections, while ERRs were similar for both doses. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN57714676.

Helminth and intestinal protozoa infections, multiparasitism and risk factors in Champasack province, Lao People's Democratic Republic.

BACKGROUND: Detailed investigations of multiparasitism are scarce in the Mekong River basin. We assessed helminth (trematode, nematode, and cestode), and intestinal protozoa infections, and multiparasitism in random population samples from three different eco-epidemiological settings in Champasack province, southern Lao People's Democratic Republic (Lao PDR), and determined underlying risk factors. METHODOLOGY: Two stool samples were collected from 669 individuals aged ≥ 6 months over consecutive days and examined for helminth infections using the Kato-Katz method. Additionally, one stool sample per person was subjected to a formalin-ethyl acetate concentration technique for diagnosis of helminth and intestinal protozoa infections. Questionnaires were administered to obtain individual and household-level data pertaining to behavior, demography and socioeconomic status. Risk factors for hepato-biliary and intestinal parasitic infections and multiparasitism were determined using multiple logistic regressions analyses. PRINCIPAL FINDINGS: MULTIPLE SPECIES INTESTINAL PARASITE INFECTIONS WERE COMMON: 86.6% of the study participants harbored at least two and up to seven different parasites concurrently. Regarding nematode infections, hookworm was the most prevalent species (76.8%), followed by Ascaris lumbricoides (31.7%) and Trichuris trichiura (25.0%). Regarding trematodes, Opisthorchis viverrini and Schistosoma mekongi infections were found in 64.3% and 24.2% of the participants, respectively. Infections with intestinal protozoa were rare. CONCLUSIONS/SIGNIFICANCE: There is a pressing need to intensify and sustain helminth control interventions in the southern part of Lao PDR. Given the high prevalence with nematode and trematode infections and the extent of multiparasitism, preventive chemotherapy is warranted. This intervention should be coupled with health education and improved access to clean water and adequate sanitation to consolidate morbidity control and enhance sustainability.