American Journal of Tropical Medicine and Hygiene最新文献

The immune response to malaria vaccines is generally stronger in malaria-naive individuals than in those with lifelong exposure. The immunological basis for this is unclear. IgM, total IgG, and IgG subclass (IgG1, IgG2, IgG3, and IgG4) antibody responses against 21 pre-erythrocytic and erythrocytic Plasmodium falciparum proteins before and after controlled human malaria infection (CHMI) via the direct venous inoculation of 3,200 P. falciparum sporozoites (PfSPZ) were compared in three groups of volunteers: 1) malaria-naïve (n = 22); 2) malaria-naïve immunized with a PfSPZ chemoattenuated vaccine (PfSPZ-CVac) (n = 27); and 3) lifelong malaria-exposed individuals from Africa (n = 20), including those with normal hemoglobin (n = 11) or sickle cell trait (n = 9). Before and after CHMI, PfSPZ-CVac-immunized individuals exhibited higher levels of IgM and IgG to CSP and SSP-2/TRAP than the other two groups. Malaria-experienced Africans exhibited more intense and broader antibody responses to blood-stage (BS) antigens than naïve and vaccinated individuals, longer pre-patent periods (PPPs), and fewer symptoms. Among confirmed malaria cases, cytophilic IgG1 and IgG3 antibodies to BS antigens were positively associated with longer PPPs, whereas IgG2, IgG4, and IgM were not. IgG2 and IgG4 (noncytophilic) P. falciparum-specific antibodies were higher in the semi-immune group, including elevated anti-CSP IgG4 (regulatory) levels. The IgM response in African volunteers post-CHMI was stronger than that in malaria-naïve and vaccinated individuals and had the hallmark of a secondary memory response. Cytophilic immunoglobulins controlled parasitaemia better than noncytophilic immunoglobulins. However, elevation of the latter in lifelong malaria-exposed individuals could be associated with regulatory responses and hamper vaccine efficacy.

On the basis of the findings of Austrian psychiatrist Julius Wagner-Jauregg, malaria fever therapy became the standard treatment for end-stage syphilis associated with generalized paralysis in the early 20th century. The parasitological and clinical features of iatrogenically induced Plasmodium vivax malaria in patients with schizophrenia and neurosyphilis during the 1950s and 1960s in Vienna, Austria, are described in the current study. All patients treated for schizophrenia or neurosyphilis at the Department of Psychiatry of the General Hospital of Vienna between 1951 and 1969 who underwent malaria fever therapy were analyzed regarding the parasitological and clinical characteristics of induced malaria. A total of 322 patients who underwent malaria fever therapy were included in the analysis (schizophrenia: n = 147; neurosyphilis: n = 175). The route of inoculation was mainly intravenous, and the dose varied between 4 and 8 mL of blood. The first fever peaks appeared ∼7 days post-inoculation. Temperature increased over time in consecutive fever paroxysms, whereas the afebrile time interval between fever peaks shortened progressively from 41 to 31 hours. After a mean of 5-6 fever peaks, all patients received standard antimalarial therapy with quinine monotherapy or combination therapy. These data reveal that the extra-hepatic incubation period of P. vivax is ∼7 days after intravenous inoculation. The current study reveals a surprisingly short periodicity between fever paroxysms, shedding light on the natural course of infection. The evaluation of historic patient data from malaria fever therapy provides a unique opportunity to study the clinical and parasitological features of untreated malaria.

Distribution of azithromycin to children ages 0-9 years old is an established strategy for treating and preventing trachoma. Our study aimed to determine whether the order in which children show up for trachoma screening is correlated with their infection status. We used baseline visit data from the study Kebele Elimination of Trachoma for Ocular Health in Ethiopia. All children ages 0-9 years old in 20 randomly selected villages were tested for ocular Chlamydia trachomatis with polymerase chain reaction. We used mixed effects logistic regression to estimate the odds ratio (OR) of trachoma positivity on presentation day 1 versus later, with village as a random effect. There was no statistical difference between infection prevalence among children measured on day 1 versus those measured during the following days (OR = 0.89-fold, 95% CI: 0.65- to 1.21-fold, P = 0.44), indicating that presentation order is not a considerable factor in highly prevalent regions.

Increased enterocyte turnover, microbial translocation, and systemic inflammation have been demonstrated to serve as predictors of morbidity and mortality in people with HIV (PWH) receiving antiretroviral therapy. Both HIV and intestinal parasitic infections cause gut damage and increased microbial translocation. A prospective cohort study of foreign-born PWH with undetectable HIV RNA (<20 copies/mL) with and without intestinal parasitic coinfection was conducted. Biomarkers of enterocyte turnover (intestinal fatty acid binding protein [IFABP]), microbial translocation (soluble cluster of differentiation [CD]14), and systemic inflammation (soluble CD163) were measured. Stool parasite real-time quantitative polymerase chain reaction (qPCR) testing and Strongyloides stercoralis recombinant IgG ELISA (Strongy IgG) were used to diagnose parasitic infection. Of the 52 participants, 14 (27%) tested positive for infection with Strongyloides stercoralis by Strongy IgG, and five (11%) of the 45 participants who provided stool samples tested positive for a parasitic infection (not including Blastocystis) by stool qPCR. The median soluble CD (sCD)14 level in PWH with positive Strongy IgG results was significantly higher than in those with negative Strongy IgG results (1.69 µg/mL versus 1.48 µg/mL; P = 0.03). Soluble CD163 and IFABP levels did not differ significantly between groups. Participants with positive Strongy IgG results demonstrated an increase of 63.4 CD4+ T cells/µL (-161 to 195) after 316.2 (87 to 625) days after strongyloidiasis treatment (P = 0.035). Participants with both HIV and an intestinal parasite infection exhibited increased levels of sCD14, a marker of microbial translocation that has been shown to be an independent predictor of mortality in PWH, compared with those without parasitic infections. Interestingly, CD4+ T cells increased after strongyloidiasis treatment.

For children in low-resource settings, repeated exposure to enteric pathogens, including through unsafe water, can have long-term effects and is potentially associated with impaired cognitive development. Access to effective, low-cost point-of-use (POU) water treatment technologies may therefore improve cognitive function. A community-based randomized controlled trial of two POU water treatment technologies was conducted in rural Limpopo, South Africa. In total, 404 households with a primary study child younger than 3 years were randomly assigned to one of four groups: 1) a silver-impregnated ceramic filter and a silver-impregnated ceramic tablet group, 2) a silver-impregnated ceramic tablet only group, 3) a safe-storage water container group, or 4) a no-intervention group. Follow-up surveys were conducted every quarter for the following 2 years. Approximately 2 years after the baseline assessment, 236 of the primary study children were evaluated using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III) examination to estimate the effects of the water treatment technologies on cognitive function. There was no significant difference found in WPPSI-III composite scores between intervention groups, and the individual presence of enteric pathogens at enrollment, reported diarrhea, and water service level exhibited no associations with WPPSI-III scores after controlling for covariates. However, several sociodemographic variables were significant predictors of cognitive function within the study population. These results are consistent with the lack of significant effects of the interventions on more proximal outcomes, such as enteric infections, diarrhea, and growth stunting, for the same study population, despite significant improvements in microbial water quality.

The chronic phase of individuals infected with Trypanosoma cruzi is characterized by low parasitemia. Blood donors in endemic and some nonendemic countries are screened for antibodies against the parasite. Data on the parasitemia of individuals identified via serological tests, as well as the risk of transfusion transmission if the screening process fails to detect infected individuals, are scarce. The potential of culturing parasites during the chronic phase increases if blood collections are performed at least three times. Sequential hemoculture (three blood collections over 3 consecutive months) was performed in 26 blood donor candidates identified as infected using serology screening and in 23 infected individuals from outpatient clinics. Each blood sample was aliquoted into six tubes for culture. At least one culture yielded a positive result in 16 of 26 (61.5%) blood donors and in 13 of 23 (56.5%) of infected controls, resulting in an overall positivity rate of 29 of 49 (59.2%). There was a relationship between the positivity of cultures and the number of positive tubes. All type B blood donors (n = 6) had positive hemoculture results, whereas only half of the type A and O donors had positive results (n = 10; P = 0.02). The number of positive tubes was also higher in this group. The implications of this finding are unclear. The analysis revealed no relationship between antibody concentration levels and the presence of positive hemoculture results. In conclusion, more than half of the infected blood donors could potentially transmit T. cruzi to recipients. This highlights the importance of blood donor screening programs for Chagas disease, even in nonendemic regions.

With an estimated 5% of global cases, Uganda carries the third-largest burden of malaria. Despite years of focus on malaria by Uganda's Ministry of Health, the malaria incidence rate increased from 206 to 271 cases per 1,000 population between 2012 and 2022. We aimed to identify gaps in malaria prevention, detection, and response in the high-burden Elgon region of Uganda. We collected data from the Ugandan District Health Information Software 2 database to identify districts with the highest incidence of malaria within the Elgon region. We used a structured assessment tool to conduct key informant interviews of district health officers, malaria focal persons, and vector control officers within each district. Qualitative data were analyzed using immersion-crystallization methodology, with multiple independent reviewers extracting major and minor themes within the framework of prevention, detection, and response. Within the category of prevention, the main theme was a lapse in vector control strategies. The major themes in the detection and response categories were lack of timely logistical support and limited chemotherapeutics, respectively. Of the 10 districts assessed, 7 (70%) had inadequate access to insecticide-treated nets, 3 (30%) had no active indoor residual spraying program, and 8 (80%) had limited or no availability of rapid diagnostic tests at the time of the assessment. The mean (±SD) time since the last resupply for antimalarial medications from the central governmental supply was 117 (±9) days. The extracted themes highlight areas for intervention within high-burden districts in eastern Uganda.