Despite increases in global Plasmodium falciparum malaria cases, a number of countries have achieved malaria elimination.1 Countries nearing elimination must often contend with both P falciparum, the ...deadliest cause of malaria in humans, and non-falciparum species like Plasmodium vivax. Primaquine and tafenoquine are the only two available anti-malarial drugs in this group, but they pose a risk of significant toxicity in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, can cause gastrointestinal side-effects, and complicate treatment regimens.3 Our understanding of G6PD deficiency's global prevalence and distribution is incomplete.4,5 G6PD screening before treatment for P vivax radical cure is recommended, though some countries use supervised 0·25 mg/kg low-dose primaquine for 14 days without screening.6 G6PD screening adds complexity to malaria control and elimination strategies, particularly in low-resource settings where P falciparum and P vivax co-exist. Malaria is caused by the Plasmodium falciparum parasite, which is transmitted into the bloodstream by mosquito bites.
To calculate prevalence estimates and evaluate the quality of studies reporting
lacking histidine-rich proteins 2 and 3, to inform an international response plan.
We searched five online databases, ...without language restriction, for articles reporting original data on
-infected patients with deletions of the
and/or
genes (
). We calculated prevalence estimates of
deletions and mapped the data by country. The denominator was all
-positive samples testing positive by microscopy and confirmed positive by species-specific polymerase chain reaction testing (PCR). If microscopy was not performed, we used the number of samples based on a different diagnostic method or PCR alone. We scored studies for risk of bias and the quality of laboratory methods using a standardized scoring system.
A total of 38 articles reporting 55 studies from 32 countries and one territory worldwide were included in the review. We found considerable heterogeneity in the populations studied, methods used and estimated prevalence of
parasites with
deletions. The derived prevalence of
deletions ranged from 0% to 100%, including focal areas in South America and Africa. Only three studies (5%) fulfilled all seven criteria for study quality.
The lack of representative surveys or consistency in study design impairs evaluations of the risk of false-negative results in malaria diagnosis due to
deletions. Accurate mapping and strengthened monitoring of the prevalence of
deletions is needed, along with harmonized methods that facilitate comparisons across studies.
Summary Background Multidrug-resistant tuberculosis threatens to reverse recent reductions in global tuberculosis incidence. Although children younger than 15 years constitute more than 25% of the ...worldwide population, the global incidence of multidrug-resistant tuberculosis disease in children has never been quantified. We aimed to estimate the regional and global annual incidence of multidrug-resistant tuberculosis in children. Methods We developed two models: one to estimate the setting-specific risk of multidrug-resistant tuberculosis among child cases of tuberculosis, and a second to estimate the setting-specific incidence of tuberculosis disease in children. The model for risk of multidrug-resistant tuberculosis among children with tuberculosis needed a systematic literature review. We multiplied the setting-specific estimates of multidrug-resistant tuberculosis risk and tuberculosis incidence to estimate regional and global incidence of multidrug-resistant tuberculosis disease in children in 2010. Findings We identified 3403 papers, of which 97 studies met inclusion criteria for the systematic review of risk of multidrug-resistant tuberculosis. 31 studies reported the risk of multidrug-resistant tuberculosis in both children and treatment-naive adults with tuberculosis and were used for evaluation of the linear association between multidrug-resistant disease risk in these two patient groups. We identified that the setting-specific risk of multidrug-resistant tuberculosis was nearly identical in children and treatment-naive adults with tuberculosis, consistent with the assertion that multidrug-resistant disease in both groups reflects the local risk of transmitted multidrug-resistant tuberculosis. After application of these calculated risks, we estimated that around 999 792 (95% CI 937 877–1 055 414) children developed tuberculosis disease in 2010, of whom 31 948 (25 594–38 663) had multidrug-resistant disease. Interpretation Our estimates underscore that many cases of tuberculosis and multidrug-resistant tuberculosis disease are not being detected in children. Future estimates can be refined as more and better tuberculosis data and new diagnostic instruments become available. Funding US National Institutes of Health, the Helmut Wolfgang Schumann Fellowship in Preventive Medicine at Harvard Medical School, the Norman E Zinberg Fellowship at Harvard Medical School, and the Doris and Howard Hiatt Residency in Global Health Equity and Internal Medicine at the Brigham and Women's Hospital.
Abstract
Hepatitis B virus (HBV) is a significant public health issue that has not been adequately addressed, especially in the high-prevalence region of Africa. Despite the incorporation of HBV ...vaccines into the Expanded Program on Immunization, children continue to be infected with HBV through maternal-to-child transmission (MTCT). The addition of a birth dose of HBV vaccine would be a cost-effective method to reduce MTCT. Birth-dose HBV vaccine policies have been adopted in the Western Pacific region but not yet in Africa. Even better protection against HBV MTCT can be achieved by treatment of pregnant women with high HBV viral loads with tenofovir. Tenofovir is already widely used in prevention of HIV MTCT (PMTCT) programs. We suggest that existing HIV PMTCT programs could be expanded to deliver care for HBV-infected pregnant women. With appropriate adoption of birth-dose vaccination policies and expansion of PMTCT programs, elimination of HBV MTCT in Africa is achievable.
Rapid diagnostic tests (RDTs) that detect histidine-rich protein 2 (PfHRP2) are used throughout Africa for the diagnosis of Plasmodium falciparum malaria. However, recent reports indicate that ...parasites lacking the pfhrp2 and/or histidine-rich protein 3 (pfhrp3) genes, which produce antigens detected by these RDTs, are common in select regions of South America, Asia, and Africa. Proving the absence of a gene is challenging, and multiple PCR assays targeting these genes have been described. A detailed characterization and comparison of published assays is needed to facilitate robust and streamlined testing approaches.
Among six pfhrp2 and pfhrp3 PCR assays tested, the lower limit of detection ranged from 0.01 pg/µL to 0.1 ng/µL of P. falciparum 3D7 strain DNA, or approximately 0.4-4000 parasite genomes/µL. By lowering the elongation temperature to 60 °C, a tenfold improvement in the limit of detection and/or darker bands for all exon 1 targets and for the first-round reaction of a single exon 2 target was achieved. Additionally, assays targeting exon 1 of either gene yielded spurious amplification of the paralogous gene. Using these data, an optimized testing algorithm for the detection of pfhrp2- and pfhrp3-negative P. falciparum is proposed.
Surveillance of pfhrp2- and pfhrp3-negative P. falciparum requires careful laboratory workflows. PCR-based testing methods coupled with microscopy and/or antigen testing serve as useful tools to support policy development. Standardized approaches to the detection of pfhrp2- and pfhrp3-negative P. falciparum should inform efforts to define the impact of these parasites.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The performance of commonly used assays for diagnosis of syphilis varies considerably depending on stage of infection and sample type. In response to the need for improved syphilis diagnostics, we ...develop assays that pair PCR pre-amplification of the tpp47 gene of Treponema pallidum subsp. pallidum with CRISPR-LwCas13a. The PCR-LwCas13a assay achieves an order of magnitude better analytical sensitivity than real-time PCR with equivalent specificity. When applied to a panel of 216 biological specimens, including 135 clinically confirmed primary and secondary syphilis samples, the PCR-LwCas13a assay demonstrates 93.3% clinical sensitivity and 100% specificity, outperforming tpp47 real-time PCR and rabbit-infectivity testing. We further adapt this approach to distinguish Treponema pallidum subsp. pallidum lineages and identify genetic markers of macrolide resistance. Our study demonstrates the potential of CRISPR-based approaches to improve diagnosis and epidemiological surveillance of syphilis.
Yaws affects children in tropical regions, while syphilis primarily affects sexually active adults worldwide. Despite various campaigns towards the eradication of yaws and elimination of syphilis, ...these two diseases are still present in Ghana. The aetiological agents of both diseases, two Treponema pallidum subspecies, are genetically similar. This study aimed to assess the prevalence of these treponematoses and the occurrence of pathogens causing similar skin lesions in the Ashanti region of Ghana. A point-of-care test was used to determine the seroprevalence of the treponematoses. Both yaws and syphilis were identified in the Ashanti region of Ghana. Multiplex PCR was used to identify treponemes and other pathogens that cause similar skin lesions. The results indicated that the seroprevalences of T. pallidum in individuals with yaws-like and syphilis-like lesions were 17.2% and 10.8%, respectively. Multiplex PCR results showed that 9.1%, 1.8% and 0.9% of yaws-like lesions were positive for Haemophilus ducreyi, herpes simplex virus-1 (HSV-1) and T. pallidum respectively. Among syphilis-like lesions, 28.3% were positive for herpes simplex virus -2 (HSV-2) by PCR. To our knowledge, this is the first time HSV-I and HSV-2 have been reported from yaws-like and syphilis-like lesions, respectively, in Ghana. The presence of other organisms apart from T. pallidum in yaws-like and syphilis-like lesions could impede the total healing of these lesions and the full recovery of patients. This may complicate efforts to achieve yaws eradication by 2030 and the elimination of syphilis and warrants updated empirical treatment guidelines for skin ulcer diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Democratic Republic of the Congo (DRC) harbors 11% of global malaria cases, yet little is known about the spatial and genetic structure of the parasite population in that country. We sequence ...2537 Plasmodium falciparum infections, including a nationally representative population sample from DRC and samples from surrounding countries, using molecular inversion probes - a high-throughput genotyping tool. We identify an east-west divide in haplotypes known to confer resistance to chloroquine and sulfadoxine-pyrimethamine. Furthermore, we identify highly related parasites over large geographic distances, indicative of gene flow and migration. Our results are consistent with a background of isolation by distance combined with the effects of selection for antimalarial drug resistance. This study provides a high-resolution view of parasite genetic structure across a large country in Africa and provides a baseline to study how implementation programs may impact parasite populations.
Reports suggest non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa but their epidemiology is ill-defined, particularly in highly malaria-endemic regions. We ...estimated incidence and prevalence of PCR-confirmed non-falciparum and Plasmodium falciparum malaria infections within a longitudinal study conducted in Kinshasa, Democratic Republic of Congo (DRC) between 2015-2017. Children and adults were sampled at biannual household surveys and routine clinic visits. Among 9,089 samples from 1,565 participants, incidences of P. malariae, P. ovale spp., and P. falciparum infections by 1-year were 7.8% (95% CI: 6.4%-9.1%), 4.8% (95% CI: 3.7%-5.9%) and 57.5% (95% CI: 54.4%-60.5%), respectively. Non-falciparum prevalences were higher in school-age children, rural and peri-urban sites, and P. falciparum co-infections. P. falciparum remains the primary driver of malaria in the DRC, though non-falciparum species also pose an infection risk. As P. falciparum interventions gain traction in high-burden settings, continued surveillance and improved understanding of non-falciparum infections are warranted.
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