Evaluation of prevalence's of pfdhfr and pfdhps mutations in Angola

<p>Abstract</p> <p>Background</p> <p>Malaria is the major cause of morbidity and mortality in Angola. The most vulnerable groups to <it>Plasmodium falciparum </it>infection are pregnant women and children under five years of age. The use of an intermittent preventive treatment (IPT) with sulphadoxine/pyrimethamine (SP) in pregnant women was introduced in Angola in 2006 by the National Malaria Control Programme, and currently this strategy has been considered to be used for children malaria control. Considering the previous wide use of SP combination in Angola, together to the reported cases of SP treatment failure it is crucial the evaluation of the prevalence of five mutations in <it>pfdhfr </it>and <it>pfdhps </it>genes associated to <it>P</it>. <it>falciparum </it>resistance to SP before the introduction of S/P IPT in children.</p> <p>Methods</p> <p>The study was conducted in five provinces, with different transmission intensities: Huambo, Cabinda, Uíge, Kwanza Norte, and Malanje. The detection of the mutations in <it>pfdhfr </it>and <it>pfdhps </it>genes was carried out in 452 <it>P</it>. <it>falciparum </it>blood samples by PCR RFLP.</p> <p>Results</p> <p>For <it>pfdhfr </it>gene, 90,3% of the samples carried the mutation 51<b>I</b>, with 7.5% of mixed infections; 51% carried wild type allele 59<b>C</b>, with 29.2% mixed infections and; 99.1% of isolates harboured the mutant allele 108<b>N</b>. Concerning, <it>pfdhps </it>gene, 83,1% were mutant type 437<b>G </b>with 11% mixed infections , while 87% of the studied isolates were wild type for codon 540.</p> <p>Discussion</p> <p>This is the first representative epidemiological study of the whole Angola country on the prevalence of the genotypes associated with SP chemoresistance. A high frequency of individual mutations in both genes (51<b>I </b>and 108<b>N </b>in <it>pfdhfr</it>, and 437<b>G </b>in <it>pfdhps</it>) was found, besides a low prevalence of the quintuple mutation.</p> <p>Conclusion</p> <p>The data showed that the implementation IPT using SP in children needs to be reviewed.</p

Dengue virus among HIV-infected pregnant women attending antenatal care in Luanda, Angola: an emerging public health concern

The dissemination of the dengue virus (DENV) in endemic regions with HIV is a public health concern with greater importance when there is evidence of vertical transmission of DENV during pregnancy. Herein, we investigated DENV among HIV-infected pregnant women in Luanda, the capital city of Angola. This was part of a cross-sectional study carried out on 42 pregnant women newly diagnosed with HIV. A total of 36 plasma samples from the 42 HIV-positive pregnant women were screened for DENV using RT‐PCR and ELISA. None of the specimens tested positive for DENV by RT-PCR. Regarding seroprevalence, 94.4% of the samples were positive for IgG and 11.1% for IgM. Recent infection (IgG-/IgM+ or IgG+/IgM+) was detected in 11.1% of the samples and past infection (IgG+/IgM-) in 83.3%. The risk of recent infection was higher in pregnant women over 25 years of age [OR: 13.0 (95% CI: 1.14-148), p=0.039]. Our study showed laboratory evidence of a recent DENV infection among HIV-infected pregnant women attending antenatal care in Luanda. Our findings provide critical data regarding DENV infection among HIV-infected pregnant women in Luanda. Future studies involving a larger sample size of HIV-infected pregnant women are necessary to support ongoing public health programs to combat arboviruses in Angola.info:eu-repo/semantics/publishedVersio

drug interactions and implications on the ubiquitin/proteasome system

Antimalarial drug resistance remains a major obstacle in malaria control. Evidence from Southeast Asia shows that resistance to artemisinin combination therapy (ACT) is inevitable. Ethnopharmacological studies have confirmed the efficacy of curcumin against Plasmodium spp. Drug interaction assays between curcumin/piperine/chloroquine and curcumin/piperine/artemisinin combinations and the potential of drug treatment to interfere with the ubiquitin proteasome system (UPS) were analyzed. In vivo efficacy of curcumin was studied in BALB/c mice infected with Plasmodium chabaudi clones resistant to chloroquine and artemisinin, and drug interactions were analyzed by isobolograms. Subtherapeutic doses of curcumin, chloroquine, and artemisinin were administered to mice, and mRNA was collected following treatment for RT-PCR analysis of genes encoding deubiquitylating enzymes (DUBs). Curcumin was found be nontoxic in BALB/c mice. The combination of curcumin/chloroquine/piperine reduced parasitemia to 37% seven days after treatment versus the control group's 65%, and an additive interaction was revealed. Curcumin/piperine/artemisinin combination did not show a favorable drug interaction in this murine model of malaria. Treatment of mice with subtherapeutic doses of the drugs resulted in a transient increase in genes encoding DUBs indicating UPS interference. If curcumin is to join the arsenal of available antimalarial drugs, future studies exploring suitable drug partners would be of interest.publishersversionpublishe

NDVI and LST extraction of MODIS data under a GIS open source application - Rickettsia study case in Angola

Fevers of unknown origin can have different aetiologies. The overlapping symptomatology of rickettsial infection and other endemic diseases that cause fever leads to a misdiagnosis or under-diagnosis of spotted fever group of Rickettsia (SFGR). To better understand the epidemiology of this vector-borne disease in Angola, a comprehensive seroprevalence study was conducted investigating the exposure to SFGR in a sample of 92 febrile, Malaria and Yellow Fever negative human plasma specimen, collected to the study of the national surveillance of febrile syndromes between 2016 and 2017, in Angola. The seroprevalence of IgG antibodies against SFG Rickettsia in humans was calculated by gender, and aimag (province). All data were analyzed through a logistic regression. Spatial data sources included Normalized Differential Vegetation Index (NDVI) and Land Surface Temperature (LST) products by Moderate Resolution Imaging Spectroradiometer (MODIS). The main objective of this work was the development of a GIS open source application to automatize the extraction of LST and NDVI products from MODIS images. The application was created as a simple graphic interface composed by two input fields (the text file with the coordinates of the sampling points (in sinusoidal coordinate system and the folder with the MODIS images), the field to define the buffer distance, and the output file. The application was tested considering MOD11A1 (LST product), MOD13Q1 and MYD13Q1 (NDVI product), free download from the USGS. QGIS 2.18.17 was used for geospatial operations and Python language was employed for the development of the GIS open source application under QGIS software. The process includes the circumscription of the major clusters where human data were collected. Then, a convex hull (minimum convex bounding geometry) was created around each sampling site with a 10 km buffer zone to accommodate the mobility among the nomadic people being samples. Counts of seropositive and seronegative humans were calculated within each of these sampling clusters along with the mean, maximum, and minimum values of NDVI and LST, and percent area of each land cover class. The application was tested in a set of 92 points in Angola and a buffer of 10 km considering the Universal transverse Mercator (UTM) Zone 33S projection (EPSG:32733) was applied for each point. The LST and NDVI statistical values were extracted for each sampling cluster. Variations in ecological niches, abundance of vegetation and land surface temperature, for ticks and fleas between different provinces could be in part responsible for the geographic differences in seroprevalence observed with SFGR.A91F-E8B8-FA62 | Teresa Susana Letra MateusN/

A Cross-Sectional Study

Funding Information: This research was funded by Abbott Rapid Diagnostics Group. The study sponsors had no role in the design of the study. Publisher Copyright: © 2024 by the authors.Rotavirus group A (RVA) is a major cause of pediatric acute gastroenteritis (AGE). Vaccination is an effective public health strategy and Angola implemented it in 2014. This hospital-based study aimed to estimate the prevalence of RVA infection and the severity of AGE in children under five years of age treated at six hospitals in Luanda Province. Between April 2021 and May 2022, 1251 fecal samples were screened by an immunochromatographic rapid test (SD Bioline). Data on socio-demographic profile, nutritional status, and clinical assessment were obtained. The association of RVA infection and AGE severity with possible risk factors was evaluated with a binary logistic regression model. Overall, the detection rate was 57.8% and girls tend to be more often infected than boys (55.2%). Infection was more common in the youngest group (1 to 6 months, 60.3%). Important sources of RVA infection were drinking water kept in tanks (57.9%) and private sanitary facilities with piped water (61%). Surprisingly, according to the Vesikari Scale score, the most severe symptoms were observed in children vaccinated with two doses (80.7%). RVA prevalence remains high despite vaccination, and further studies should address the association between infection sources and disease severity, as well as the causes underlying vaccine (un)effectiveness.publishersversionpublishe

Plasmodium chabaudi chabaudi malaria parasites can develop stable resistance to atovaquone with a mutation in the cytochrome b gene

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum</it>, has developed resistance to many of the drugs in use. The recommended treatment policy is now to use drug combinations. The atovaquone-proguanil (AP) drug combination, is one of the treatment and prophylaxis options. Atovaquone (ATQ) exerts its action by inhibiting plasmodial mitochondria electron transport at the level of the cytochrome bc1 complex. <it>Plasmodium falciparum in vitro </it>resistance to ATQ has been associated with specific point mutations in the region spanning codons 271-284 of the <it>cytochrome b </it>gene. ATQ -resistant <it>Plasmodium yoelii </it>and <it>Plasmodium berghei </it>lines have been obtained and resistant lines have amino acid mutations in their CYT <it>b </it>protein sequences. <it>Plasmodium chabaudi </it>model for studying drug-responses and drug-resistance selection is a very useful rodent malaria model but no ATQ resistant parasites have been reported so far. The aim of this study was to determine the ATQ sensitivity of the <it>P. chabaudi </it>clones, to select a resistant parasite line and to perform genotypic characterization of the <it>cytb </it>gene of these clones.</p> <p>Methods</p> <p>To select for ATQ resistance, <it>Plasmodium. chabaudi chabaudi </it>clones were exposed to gradually increasing concentrations of ATQ during several consecutive passages in mice. <it>Plasmodium chabaudi cytb </it>gene was amplified and sequenced.</p> <p>Results</p> <p>ATQ resistance was selected from the clone AS-3CQ. In order to confirm whether an heritable genetic mutation underlies the response of AS-ATQ to ATQ, the stability of the drug resistance phenotype in this clone was evaluated by measuring drug responses after (i) multiple blood passages in the absence of the drug, (ii) freeze/thawing of parasites in liquid nitrogen and (iii) transmission through a mosquito host, <it>Anopheles stephensi</it>. ATQ resistance phenotype of the drug-selected parasite clone kept unaltered. Therefore, ATQ resistance in clone AS-ATQ is genetically encoded. The Minimum Curative Dose of AS-ATQ showed a six-fold increase in MCD to ATQ relative to AS-3CQ.</p> <p>Conclusions</p> <p>A mutation was found on the <it>P. chabaudi cytb </it>gene from the AS-ATQ sample a substitution at the residue Tyr268 for an Asn, this mutation is homologous to the one found in <it>P. falciparum </it>isolates resistant to ATQ.</p

Insights into SARS-CoV-2 in Angola during the COVID-19 peak: molecular epidemiology and genome surveillance

Background: In Angola, COVID-19 cases have been reported in all provinces, resulting in >105,000 cases and >1900 deaths. However, no detailed genomic surveillance into the introduction and spread of the SARS-CoV-2 virus has been conducted in Angola. We aimed to investigate the emergence and epidemic progression during the peak of the COVID-19 pandemic in Angola. Methods: We generated 1210 whole-genome SARS-CoV-2 sequences, contributing West African data to the global context, that were phylogenetically compared against global strains. Virus movement events were inferred using ancestral state reconstruction. Results: The epidemic in Angola was marked by four distinct waves of infection, dominated by 12 virus lineages, including VOCs, VOIs, and the VUM C.16, which was unique to South-Western Africa and circulated for an extended period within the region. Virus exchanges occurred between Angola and its neighboring countries, and strong links with Brazil and Portugal reflected the historical and cultural ties shared between these countries. The first case likely originated from southern Africa. Conclusion: A lack of a robust genome surveillance network and strong dependence on out-of-country sequencing limit real-time data generation to achieve timely disease outbreak responses, which remains of the utmost importance to mitigate future disease outbreaks in Angola

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

NDVI and LST extraction of MODIS data under a GIS open source application - Rickettsia study case in Angola

Fevers of unknown origin can have different aetiologies. The overlapping symptomatology of rickettsial infection and other endemic diseases that cause fever leads to a misdiagnosis or under-diagnosis of spotted fever group of Rickettsia (SFGR). To better understand the epidemiology of this vector-borne disease in Angola, a comprehensive seroprevalence study was conducted investigating the exposure to SFGR in a sample of 92 febrile, Malaria and Yellow Fever negative human plasma specimen, collected to the study of the national surveillance of febrile syndromes between 2016 and 2017, in Angola. The seroprevalence of IgG antibodies against SFG Rickettsia in humans was calculated by gender, and aimag (province). All data were analyzed through a logistic regression. Spatial data sources included Normalized Differential Vegetation Index (NDVI) and Land Surface Temperature (LST) products by Moderate Resolution Imaging Spectroradiometer (MODIS). The main objective of this work was the development of a GIS open source application to automatize the extraction of LST and NDVI products from MODIS images. The application was created as a simple graphic interface composed by two input fields (the text file with the coordinates of the sampling points (in sinusoidal coordinate system and the folder with the MODIS images), the field to define the buffer distance, and the output file. The application was tested considering MOD11A1 (LST product), MOD13Q1 and MYD13Q1 (NDVI product), free download from the USGS. QGIS 2.18.17 was used for geospatial operations and Python language was employed for the development of the GIS open source application under QGIS software. The process includes the circumscription of the major clusters where human data were collected. Then, a convex hull (minimum convex bounding geometry) was created around each sampling site with a 10 km buffer zone to accommodate the mobility among the nomadic people being samples. Counts of seropositive and seronegative humans were calculated within each of these sampling clusters along with the mean, maximum, and minimum values of NDVI and LST, and percent area of each land cover class. The application was tested in a set of 92 points in Angola and a buffer of 10 km considering the Universal transverse Mercator (UTM) Zone 33S projection (EPSG:32733) was applied for each point. The LST and NDVI statistical values were extracted for each sampling cluster. Variations in ecological niches, abundance of vegetation and land surface temperature, for ticks and fleas between different provinces could be in part responsible for the geographic differences in seroprevalence observed with SFGR.Joana Afonso and Jocelyne Neto, Instituto Nacional de Saúde Pública, Ministério da Saúde, Maianga-Luanda, Angola for the support. USGS for satellite data

HIV, hepatitis B virus, hepatitis C virus, and syphilis among pregnant women attending antenatal care in Luanda, Angola: seroprevalence and risk factors

Fundação para a Ciência e a Tecnologia, Grant/Award Number: SFRH/BD/135296/2017Infectious diseases during pregnancy remain a public health concern, especially in a resource-limited setting. The study aimed to determine the seroprevalence and determinants of HIV and co-infection with hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis among pregnant women attending antenatal care in Luanda, the capital city of Angola. A cross-sectional study was conducted with 1612 pregnant women screened for HIV during antenatal care. HIV-reactive were also screened for the HBV, HCV, and syphilis using immunoassay kits. A logistic regression model, adjusted odds ratios (AOR) and their 95% confidence interval (CI) were calculated with a level of significance set at 5%. The overall seroprevalence of HIV was 2.6%. About 13% of HIV-positive pregnant women were coinfected. From which, 7.5% were reactive to HBV and 5% to syphilis. There was no reactivity to HCV. Pregnant women younger aged than 25 years were significantly protected from HIV-infection (AOR, 0.43 [95% CI, 0.20-0.91], P = .026). The co-infection was 1.3 times (AOR, 0.04-41.0) in younger aged than 25 years, 7.0 times (AOR, 0.50-99.2) to residents in urbanized areas, and 1.4 times (AOR, 0.10-20.9) in pregnant women with a high educational level. In conclusion, infectious diseases are a public health burden among pregnant women in Luanda. However, include an integrated antenatal screening mainly in urbanized areas is crucial to reduce the spread of infectious diseases in different communities of Angola.info:eu-repo/semantics/publishedVersio