Transactions of The Royal Society of Tropical Medicine and Hygiene最新文献

Background: Deployment of seasonal malaria chemoprevention (SMC) for young children using monthly sulphadoxine-pyrimethamine-amodiaquine (SPAQ) has recently been extended to Central and East Africa.

Methods: A pilot pharmacometric assessment was nested within a larger deployment of SMC in a high malaria transmission area in northern Mozambique. SPAQ was given to 460 healthy children in two large villages. Simultaneous filter-paper blood spot malaria quantitative PCRs, blood slide microscopy and antimalarial drug measurements were taken before, then 7 and 28 d after first SPAQ administration.

Results: After SPAQ, parasitaemia prevalence decreased from 68% to 41%. Among children followed successfully for 28 d, malaria parasitaemia prevalence declined from 71% to 44%. Preventive efficacy was 97% for Plasmodium ovale and 42% for Plasmodium falciparum. Reinfections (N=50 with sufficient DNA for genotyping) and recrudescences (N=3) often grew through high concentrations of desethylamodiaquine, yet all 250 P. falciparum isolates genotyped were Pfcrt 76K, a molecular marker of 4-aminoquinoline susceptibility. One-third (21/64) of microscopy-detectable breakthrough P. falciparum infections had patent gametocytaemia. There was a clear chemoprevention exposure-response relationship evident for desethylamodiaquine, but not for sulphadoxine or pyrimethamine.

Conclusions: In Nampula, northern Mozambique, amodiaquine had low parasitological efficacy and sulphadoxine and pyrimethamine did not contribute significantly to chemoprevention.

Background: Crimean-Congo haemorrhagic fever (CCHF) is a severe tick-borne viral infection with a high mortality rate. The multi-inflammatory index (MII), consisting of MII-1, MII-2 and MII-3, has been proposed as a prognostic biomarker in infectious diseases. However, its role in CCHF prognosis remains unclear.

Methods: This retrospective observational study analysed 290 CCHF patients admitted to Erzurum Regional Training and Research Hospital between January 2019 and September 2024. The MIIs were calculated from blood samples obtained on the day of hospital admission. Patients were categorized based on mortality outcomes, and logistic regression and receiver operating characteristics curve analyses were conducted to assess the predictive value of the MIIs.

Results: Mortality occurred in 9.31% of patients, with significantly higher MII-1, MII-2 and MII-3 levels in non-survivors. MII-1 showed the highest predictive accuracy (area under the curve 0.846, sensitivity 88%, specificity 75%). No significant difference was found in ribavirin administration between survivors and non-survivors.

Conclusions: MIIs, particularly MII-1, serve as independent predictors of mortality in CCHF patients. Early evaluation of MII levels may aid risk stratification and clinical decision-making. Future studies should explore the dynamic changes in these indices and their impact on treatment outcomes.

Plasmodium vivax is the most prevalent malaria parasite in Brazil, accounting for approximately 85% of annual malaria cases. Therapeutic failure in malaria has been associated with host genetic factors that influence drug metabolism. This study aimed to evaluate the impact of Cytochrome P450 gene polymorphisms on the treatment of Plasmodium vivax malaria in Brazil. A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement. Studies were screened based on title and abstract, duplicates were removed and articles published up to August 2024 were considered. Full-text eligibility and risk of bias assessments were performed. Allelic frequencies of the identified polymorphisms were extracted from the selected studies and visualised using pie charts. Of 296 studies retrieved, eight met the inclusion criteria. Most studies focused on the association between CYP2D6 polymorphisms and malaria treatment failure, employing a genotype-based approach to predict metaboliser phenotypes. Overall, the review revealed a lack of consensus regarding the relationship between Cytochrome P450 single nucleotide polymorphisms and antimalarial drug response. The potential implications of CYP450 genetic variability for therapeutic failure and treatment safety in Brazil are discussed.

Background: Hepatitis A virus (HAV) and hepatitis E virus (HEV) continue to represent a significant global public health challenge. This study aims to assess the seroprevalence of anti-HAV immunoglobulin G (IgG) and anti-HEV IgG antibodies among blood donors in Paraguay, a region where epidemiological data on these infections are scarce.

Methods: Serum samples were collected from 452 blood donors in five regions of Paraguay and the presence of anti-HAV IgG and anti-HEV IgG antibodies was assessed.

Results: Overall, 68.1% of donors tested positive for anti-HAV IgG, with a higher prevalence in older age groups (p<0.001) and significant regional differences (p<0.001). Notably, a low seroprevalence was found in the 18- to 25-y age group (36.4%), highlighting a potential gap in immunity. In contrast, anti-HEV IgG was detected in 6.0% of samples, with no significant differences observed across age groups or regions. Men exhibited a non-significant trend toward higher anti-HEV IgG seroprevalence compared with women (p=0.082).

Conclusions: The high seroprevalence of anti-HAV IgG among older blood donors contrasts sharply with low coverage in younger adults, underscoring the critical need to prioritize and expand HAV vaccination efforts in younger adults. Furthermore, the low HEV seroprevalence suggests an opportunity for proactive surveillance and prevention, potentially addressing recent introduction or limited transmission. These results offer a valuable epidemiological foundation to guide effective disease control strategies and public health programs in Paraguay.

Background: Studies relating allelic variants in toll-like receptor (TLR) genes to the parasitological profile of Plasmodium vivax malaria are scarce. Therefore, we sought to assess whether polymorphisms in these genes can influence the clinical and parasitological aspects of individuals with P. vivax malaria in an endemic area from the Brazil-French Guiana border.

Methods: We analyzed 76 patients with P. vivax malaria. Parasitological parameters were collected, and genomic DNA was extracted from whole blood. The single nucleotide polymorphisms (SNPs) of TLR4 (rs4986790, rs4986791), TLR6 (rs5743810) and TLR9 genes (rs187084, rs5743836) were genotyped by qPCR. Association between the levels of parasitemia and gametocytes with the SNPs was performed using Kruskal-Wallis and Mann-Whitney tests. Parasitemia and gametocyte levels were adjusted for the polymorphisms using a linear regression model.

Results: There was a correlation between the TLR4 rs4986790, TLR6 rs5743810 and TLR9 rs187084 SNPs and parasitological aspects.

Conclusions: The results described here suggest that these genes' polymorphisms may have a role in the development of the inflammatory response during P. vivax malaria. The potential implications of these findings are discussed.

Background: Zika virus (ZIKV) is an emergent pathogen known for the outbreak in early 2015, causing significant consequences, of which congenital ZIKV syndrome is the most severe manifestation. Toll-like receptors (TLRs) are important for the appropriate function of the innate immune response against pathogens. The presence of mutations in TLR genes can potentially result in altered susceptibility to diseases. Thus, this study aimed to investigate the influence of TLR2 rs5743708, TLR3 rs3775291, TLR4 rs4986790, TLR4 rs4986791, TLR6 rs5743810 and TLR7 rs179008 polymorphisms in ZIKV infection in a case-control study.

Methods: The study enrolled 142 patients with ZIKV that sought medical care with ZIKV-related symptoms during the ZIKV outbreak and 142 controls. Genotyping was carried out by PCR-RFLP. Multivariate and χ2 analyses were performed to assess associations between polymorphisms and disease.

Results: The dominant inheritance model revealed an increased risk for patients who were carriers of the TLR3 rs3775291 T allele. The C/T-T/T genotypes were significantly increased in patients rather than controls compared with the C/C genotype (OR=1.76, 95% CI 1.05 to 2.94; p=0.03).

Conclusions: Our data support the literature and suggest that the variant rs3775291 in TLR3 may confer susceptibility to ZIKV infection in the Brazilian population.

Background: A rich biodiversity of predators has been suggested to suppress the risk of zoonotic spillover by regulating prey abundance and behavior. We evaluated the association between predator species richness and spillover events of Ebolavirus and Marburgvirus in Africa.

Methods: Historical records of filovirus outbreaks, along with ecological, geographical and socioeconomic factors, were considered in this environmental study. We used the maximum entropy approach (Maxent modeling) and stacked species distribution models to estimate predator species richness. Logistic regression analyses accounting for spatiotemporal autocorrelations were conducted to assess the association between predator species richness and spillover risk, adjusting for potential confounders.

Results: Higher species richness of certain predators-the order Strigiformes and the family Colubridae-was associated with lower risks of Ebolavirus spillover, but not with Marburgvirus spillover. The third quartile (OR=0.02, 95% Bayesian credible interval [BCI]=0.00-0.84) and fourth quartile (OR=0.07, 95% BCI=0.00-0.42) of Strigiformes species richness, as well as the third quartile (OR=0.15, 95% BCI=0.01-0.73) and fourth quartile (OR=0.53, 95% BCI=0.03-0.85) of Colubridae species richness, were significantly associated with reduced odds of Ebolavirus index cases.

Conclusion: These findings support a possible role for predator species richness in suppressing zoonotic spillover.

Background: Early detection of nerve impairment and its progression is critical in all leprosy cases, regardless of spectrum and treatment. This study aims to identify subclinical neuropathy at presentation in newly diagnosed leprosy patients and to monitor its progression after initiating multidrug therapy (MDT) using a combination of clinical nerve palpation, small fibre neuropathy tests (e.g. vibration, temperature, touch, pain, sweat), monofilament testing (MFT), voluntary muscle testing (VMT) and nerve conduction studies (NCSs).

Methods: We studied 38 nerves among 19 patients and followed them for 12 months to assess neuropathy progression. Nerve palpation was evaluated clinically at baseline, while MFT was performed on the ulnar, median and posterior tibial nerves at baseline and 1 y. VMT and NCSs were conducted at both baseline and 12 months. Small fibre neuropathy was assessed using temperature (test tube), vibration (vibration perception threshold), sweating (starch iodide test) and pain responses at baseline.

Results: Among the study cohort, 52.6% had borderline tuberculoid leprosy, followed by lepromatous leprosy (31.5%). Seven patients (36.8%) presented with a reaction at baseline. Major nerve trunks that were thickened included the ulnar nerve (52.6%) and common peroneal nerve (31.6%). Five patients had normal NCSs at baseline and 14 (73.4%) had abnormalities at baseline through NCSs and MFT. Thickened nerves had decreased nerve conduction and amplitude at baseline and more in the lepromatous spectrum. When they were followed up, two patients improved, five had no change and seven worsened from baseline in the NCSs. One patient had an abnormal NCS when followed up from the normal baseline NCS. The pattern of neuropathy was predominantly axonal and two of them were mixed (both axonal and demyelinating). MFT, compared with NCSs, was found to help detect both small and large fibre involvement.

Conclusions: A combination of clinical tests and periodic NCSs is essential for detecting the progression of leprosy neuropathy. Neuropathy continued to progress despite 1 y of MDT, particularly in patients with early involvement at baseline.

A 20-y-old male with sickle cell trait presented with 5 days of bilateral thigh pain and soreness, without history of trauma or strenuous activity. He had elevated creatine kinase (56,179 U/L) and troponin-T (322 ng/L) levels. Nasopharyngeal swab PCR was positive for SARS-CoV-2. He presented early and had adequate fluid resuscitation during the initial phase of illness that prevented acute kidney injury and facilitated his early recovery. To the best of our knowledge, this is only the fifth case of acute rhabdomyolysis associated with COVID-19 and sickle cell trait reported in the literature, and is a less severe presentation compared with previous reports.