American Journal of Tropical Medicine and Hygiene最新文献

Biannual azithromycin administration to preschool children in sub-Saharan Africa improved childhood mortality but selected for antibiotic resistance (AMR). WHO guidelines recommended focusing treatment on infants ages 1-11 months old to reduce mortality while minimizing selection of AMR. The Infant Mortality Reduction by the Mass Administration of Azithromycin study was a double-masked, placebo-controlled, cluster-randomized trial that investigated these WHO guidelines. Health centers from three regions of Burkina Faso were randomized in a 2:1 ratio to receive either biannual azithromycin (67%) or placebo (33%) distribution to children 1-11 months old. A total of 3,524 rectal samples from children ages 1-59 months old from 60 randomly selected communities were included in the analysis. The prespecified primary outcome was the community-level fold change in macrolide resistance determinants between arms at the 24-month time point. Macrolide resistance determinants in the gut of children in communities whose infants received azithromycin did not increase compared with those in communities treated with placebo (1.05-fold change). Similarly, the fold changes for resistance determinants for beta-lactams, metronidazole, sulfonamides, tetracycline, and trimethoprim were 0.99-fold, 1.00-fold, 1.22-fold, 0.96-fold, and 0.96-fold, respectively. At 6 months after the fourth treatment, there were no detectable differences in the microbiome structure (Euclidean permutational multivariate analysis of variance) and Shannon diversity index between treatment arms. These results suggest that biannual azithromycin administration to children 1-11 months old did not lead to a significant long-lasting increase in gut AMR or alterations of the gut microbiomes of children 1-59 months old in the community.

West Nile virus lineage 1 (WNVL1) has been the only lineage known to circulate within the United States; however, multiple other lineages have been identified around the world. West Nile virus lineage 3 (WNVL3) was previously only isolated from mosquitoes in Czechia, but no human cases had been observed. West Nile virus lineage 3 was identified alongside WNVL1 in 2023 in a severely ill Nebraska patient with no history of international travel. To determine the extent of WNVL3 transmission, 1,199 historical mosquito pools collected from the state of Nebraska from 2012 through 2024 totaling >40,000 Culex spp. mosquitoes were tested. All pools tested negative for WNVL3 RNA. This study suggests that WNVL3 may circulate at very low levels or in alternative vector species in Nebraska.

Microbial translocation drives chronic immune activation that is linked to HIV disease progression. Invasive parasitic gut nematodes induce microbial translocation and downregulate the expression of pro-inflammatory cytokines. We evaluated the impact of albendazole anthelmintic therapy on serum markers of microbial translocation and inflammation among helminth-infected Ugandans living with HIV. Participants were randomized to an immediate or delayed 400 mg of daily albendazole and followed for 1 month. Baseline stool analysis, conducted via multiparallel real-time quantitative polymerase chain reaction, determined the prevalence of parasitic infections. Baseline and follow-up blood draws evaluated soluble CD14 (sCD14), C-reactive protein (CRP), and 10 pro-inflammatory cytokines. Changes in biomarker concentrations over time and across randomization arms were evaluated using parametric and nonparametric tests. We enrolled 224 antiretroviral therapy-experienced Ugandan adults living with HIV. Twenty-four participants (10.7%) were infected with either Necator americanus or Strongyloides stercoralis (12 immediate arm; 12 delayed arm). At baseline, participants with current helminth infection had increased concentrations of CRP, interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor-α compared with uninfected participants. Among helminth-infected participants, those in the immediate therapy arm had nonsignificant higher mean sCD14 concentrations (1.40 µg/mL) at follow-up compared with participants in the delayed arm (95% CI: -0.17, 2.98; P = 0.06) with no significant differences observed in other biomarker concentrations. Increases in sCD14 following anthelmintic treatment in this cohort require further investigation in larger cohorts with longer follow-up durations. However, incorporating anthelmintic therapy into routine adult HIV care may provide subtle health benefits in this potentially vulnerable population.

South Africa is one of 25 countries identified by the WHO as having the potential to eliminate malaria in the near future. In response to the emerging threat of antimalarial resistance, South Africa has enhanced its surveillance programs to enable the mapping of the prevalence of resistance markers at the facility level. A total of 4,471 samples, collected between January 2022 and August 2024 from healthcare facilities and during active surveillance in malaria-eliminating districts in KwaZulu-Natal and Mpumalanga Provinces, were assessed for drug (mutations in the kelch13, chloroquine resistance transporter [crt], multidrug resistance 1 [mdr1], dihydrofolate reductase [dhfr], and dihydropterate synthase [dhps] genes) and diagnostic (histidine-rich protein 2/3 [hrp2/3] gene deletions) resistance markers using polymerase chain reaction testing and sequencing (Sanger or targeted amplicon) protocols. Validated markers of artemisinin partial resistance were rare, with the P574L mutation detected as a minor allele in two samples and the P553L mutation present in one sample. Of the 60 additional nonsynonymous mutations detected, the A578S (30/999) and the I494V (13/951) mutations were most prevalent. Almost all parasites assessed carried the crtK76 (99.8%) and mdr1N86 (99.0%) alleles, suggesting susceptibility to chloroquine. The dhfr triple (99.9%) and dhps double (98.2%) mutations associated with pyrimethamine and sulfadoxine resistance, respectively, were close to fixation. No single or double hrp2/3 gene deletions were detected. These findings suggest that the recommended treatments and diagnostics in South Africa are effective. However, the strong selection for antimalarial drug resistance markers across southern Africa, combined with high regional interconnectedness, emphasizes the need for sustained malaria molecular surveillance to support South Africa and the southern Africa region in achieving their elimination goals.

The community-randomized, placebo-controlled Macrolides Oraux pour Réduire les Décès avec un Oeil sur la Résistance (MORDOR) trial revealed that biannual mass azithromycin distributions to preschool children reduced child mortality in sub-Saharan Africa. Other benefits may also be possible. Surveillance of local health post records was assessed from the Niger study site from 2014 to 2016. Community-level data on all clinic visits, diagnoses, and antibiotic prescriptions recorded in the health post logbooks were retrospectively extracted for the period spanning from 12 months before baseline to 12 months after baseline. During the 12-month period after the communities were randomized in the MORDOR trial, a total of 5,229 clinic visits were documented in the azithromycin group, compared with 7,647 in the placebo group (incidence rate ratio [IRR]: 0.82; 95% CI: 0.79-0.85); 2,011 malaria diagnoses were documented in the azithromycin group, compared with 3,366 in the placebo group (IRR: 0.71; 95% CI: 0.46-1.39); and 2,218 courses of antibiotics were documented in the azithromycin group, compared with 3,297 in the placebo group (IRR: 0.81; 95% CI: 0.77-0.85). The reduction in clinic visits and clinic-prescribed antibiotics is consistent with a reduction in infectious diseases in the azithromycin-treated communities.

Growing evidence implicates environmental enteric dysfunction (EED) as a driver of poor growth and neurodevelopment (ND) in early childhood. To investigate these findings, a cross-sectional study examining associations between biomarkers reflecting various domains of EED and growth and ND in Guatemalan infants was conducted. A subset of 114 cohort infants was randomly selected from a 2017-2019 population-based cohort study of 499 infants in rural southwest Guatemala. Growth and neurodevelopmental performance were assessed at a household visit at ∼13 months of age using the Mullen Scales of Early Learning (MSEL). Serum samples collected at the visit were analyzed for concentrations of biomarkers, assessing inflammation (α-1 acid glycoprotein), intestinal repair (glucagon-like peptide-2), and intestinal barrier disruption (anti-flagellin immunoglobulin A [anti-FliC IgA]). Multivariable regression analyses, adjusting for relevant confounders, were conducted to define the associations between these EED biomarkers and length-for-age z-scores (LAZ) and neurodevelopmental performance. Analyses both including and excluding infants who exhibited acute infectious disease symptoms at the time of the visit were planned. However, no significant associations were found between these biomarkers and LAZ or MSEL scores in the analysis of all children. Removing infants with acute infectious symptoms revealed an association between anti-FliC IgA and MSEL. Specifically, an increase of 10 ng/L in anti-FliC IgA concentration was associated with a decrease in the MSEL Early Learning Composite (ELC) raw score of 3.2 points, equating to approximately a nine-point decrease in the ELC standard score. Having higher levels of anti-FliC IgA may represent a significant risk to long-term health and development.

Kenya is experiencing a clade Ib mpox outbreak, with 28 confirmed cases reported by the Ministry of Health from July to December 2024. Polymerase chain reaction testing was performed for varicella zoster virus (VZV). Testing was also part of the differential diagnosis for mpox, and a subset of cases was genetically sequenced. Of 277 specimens tested for mpox, 170 (61%) tested positive for VZV, including instances of coinfection with both viruses in four cases. Genome analysis was used to identify clade 5 human alphaherpesvirus 3 in eight of the genetically sequenced cases. Expanding laboratory capacity during this outbreak enhanced disease intelligence by confirming another etiology of rash among patients who tested negative for mpox, underscoring the need for a broad differential diagnosis when diseases present with overlapping clinical signs and symptoms.

Melioidosis, caused by Burkholderia pseudomallei, is a potentially fatal bacterial infection endemic to Southeast Asia and northern Australia. The disease often resurges after extreme weather events, such as typhoons. In this study, we investigated the epidemiological trends of melioidosis in Taiwan from 2015 to 2024, focusing on the impact of typhoon-associated precipitation. A total of 396 confirmed cases were reported over the decade, with 123 cases (31.1%) occurring in 2024 alone. Statistical analysis revealed a weak but significant correlation between precipitation and melioidosis incidence (Spearman rho: 0.275, P = 0.002), whereas leptospirosis incidence exhibited a stronger correlation with rainfall (Spearman rho: 0.477, P <0.01). These findings suggest that although increased rainfall may facilitate the dissemination of B. pseudomallei, other environmental and host-related factors likely contribute to disease outbreaks. A multiple linear regression analysis was performed to identify the relationship between meteorological and socioeconomic variables and the log-transformed melioidosis incidence across regions. Among the predictors, 10-minute sustained wind speed was significantly associated with higher melioidosis incidence (β = 1.769, P = 0.025), whereas maximum wind speed showed a significant negative association (β = -1.366, P = 0.049). Given the potential influence of climate change and globalization on infectious disease transmission, continuous surveillance and proactive public health measures are essential to mitigate future outbreaks. Physicians should remain vigilant for melioidosis and leptospirosis, particularly after typhoons and among travelers returning from affected regions.

Molecular and cellular mechanisms of leptospirosis pathogenesis remain poorly understood. Recent genomic, in vitro, and animal model data indicate that the novel PF07598 gene family encodes the so-called virulence-modifying proteins (VMPs), secreted exotoxins that are hypothesized to mediate the clinical manifestations of leptospirosis. Key to understanding the mechanistic role of VMPs in disease pathogenesis is testing the hypothesis that VMPs are produced during infection. Rhesus macaques were experimentally inoculated at multiple sites with low-passage Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. Microscopic agglutination test and polymerase chain reaction confirmed infection, but animals did not develop observable illness. An ELISA using recombinant VMPs demonstrated anti-VMP IgM and IgG antibodies on days 4 and 8, respectively, indicating that the infectious strain produced VMPs expectedly after infection. An antigen-capture ELISA detected VMP antigen in infected monkey urine and blood. Liver, kidneys, and lungs demonstrated mild histopathological abnormalities, demonstrating that target organs were subclinically involved in nonsevere leptospirosis. Elevated serum levels of multiple cytokines (TNFα, IL-15, IL-8, sCD40L, MCP-1, and MIPb) showed systemic host inflammatory responses. This study addresses key gaps in understanding leptospirosis pathogenesis in nonhuman primates, aiming to develop VMP-based biomarkers for improved diagnosis and prognosis.