scholarly journals Impact of seasonal variations in Plasmodium falciparum malaria transmission on the surveillance of pfhrp2 gene deletions

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Oliver John Watson ◽  
Robert Verity ◽  
Azra C Ghani ◽  
Tini Garske ◽  
Jane Cunningham ◽  
...  
Keyword(s):  
False Negative ◽  
Plasmodium Falciparum Malaria ◽  
Rapid Diagnostic Tests ◽  
World Health ◽  
Seasonal Fluctuations ◽  
Gene Deletions ◽  
Control Programmes ◽  
Sampling Intervals ◽  
Optimum Sampling ◽  
Health Organization

Ten countries have reported pfhrp2/pfhrp3 gene deletions since the first observation of pfhrp2-deleted parasites in 2012. In a previous study (Watson et al., 2017), we characterised the drivers selecting for pfhrp2/3 deletions and mapped the regions in Africa with the greatest selection pressure. In February 2018, the World Health Organization issued guidance on investigating suspected false-negative rapid diagnostic tests (RDTs) due to pfhrp2/3 deletions. However, no guidance is provided regarding the timing of investigations. Failure to consider seasonal variation could cause premature decisions to switch to alternative RDTs. In response, we have extended our methods and predict that the prevalence of false-negative RDTs due to pfhrp2/3 deletions is highest when sampling from younger individuals during the beginning of the rainy season. We conclude by producing a map of the regions impacted by seasonal fluctuations in pfhrp2/3 deletions and a database identifying optimum sampling intervals to support malaria control programmes.

scholarly journals No evidence of false-negative Plasmodium falciparum rapid diagnostic results in Monrovia, Liberia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mandella King ◽  
Alexander E. George ◽  
Pau Cisteró ◽  
Christine K. Tarr-Attia ◽  
Beatriz Arregui ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
False Negative ◽  
Malaria Diagnosis ◽  
Rapid Diagnostic Tests ◽  
Molecular Testing ◽  
False Negatives ◽  
Gene Deletions ◽  
History Of ◽  
Catholic Hospital ◽  
Or History

Abstract Background Malaria diagnosis in many malaria-endemic countries relies mainly on the use of rapid diagnostic tests (RDTs). The majority of commercial RDTs used in Africa detect the Plasmodium falciparum histidine-rich protein 2 (PfHRP2). pfhrp2/3 gene deletions can therefore lead to false-negative RDT results. This study aimed to evaluate the frequency of PCR-confirmed, false-negative P. falciparum RDT results in Monrovia, Liberia. Methods PfHRP2-based RDT (Paracheck Pf®) and microscopy results from 1038 individuals with fever or history of fever (n = 951) and pregnant women at first antenatal care (ANC) visit (n = 87) enrolled in the Saint Joseph’s Catholic Hospital (Monrovia) from March to July 2019 were used to assess the frequency of false-negative RDT results. True–false negatives were confirmed by detecting the presence of P. falciparum DNA by quantitative PCR in samples from individuals with discrepant RDT and microscopy results. Samples that were positive by 18S rRNA qPCR but negative by PfHRP2-RDT were subjected to multiplex qPCR assay for detection of pfhrp2 and pfhrp3. Results One-hundred and eighty-six (19.6%) and 200 (21.0%) of the 951 febrile participants had a P. falciparum-positive result by RDT and microscopy, respectively. Positivity rate increased with age and the reporting of joint pain, chills and shivers, vomiting and weakness, and decreased with the presence of coughs and nausea. The positivity rate at first ANC visit was 5.7% (n = 5) and 8% (n = 7) by RDT and microscopy, respectively. Out of 207 Plasmodium infections detected by microscopy, 22 (11%) were negative by RDT. qPCR confirmed absence of P. falciparum DNA in the 16 RDT-negative but microscopy-positive samples which were available for molecular testing. Among the 14 samples that were positive by qPCR but negative by RDT and microscopy, 3 only amplified pfldh, and among these 3 all were positive for pfhrp2 and pfhrp3. Conclusion There is no qPCR-confirmed evidence of false-negative RDT results due to pfhrp2/pfhrp3 deletions in this study conducted in Monrovia (Liberia). This indicates that these deletions are not expected to affect the performance of PfHRP2-based RDTs for the diagnosis of malaria in Liberia. Nevertheless, active surveillance for the emergence of PfHRP2 deletions is required.

scholarly journals Clinical Features and Mortality Associated with Severe Malaria in Adults in Southern Mauritania

2020 ◽  
Vol 6 (1) ◽  
pp. 1
Author(s):  
Boushab Mohamed Boushab ◽  
Mohamed Salem Ould Ahmedou Salem ◽  
Ali Ould Mohamed Salem Boukhary ◽  
Philippe Parola ◽  
Leonardo Basco
Keyword(s):  
Renal Failure ◽  
Respiratory Distress ◽  
Severe Malaria ◽  
Falciparum Malaria ◽  
Clinical Features ◽  
Signs And Symptoms ◽  
Plasmodium Falciparum Malaria ◽  
Severe Anaemia ◽  
World Health ◽  
Health Organization

Severe malaria in adults is not well-studied in Sahelian Africa. Clinical features and mortality associated with severe Plasmodium falciparum malaria in adult patients hospitalized in Kiffa, southern Mauritania, were analysed. Patients over 15 years old admitted for severe malaria between August 2016 and December 2019 were included in the present retrospective study. The World Health Organization (WHO) criteria were used to define severe malaria. The presenting clinical characteristics and outcome were compared. Of 4266 patients hospitalized during the study period, 573 (13.4%) had a positive rapid diagnostic test for malaria, and 99 (17.3%; mean age, 37.5 years; range 15–79 years; sex-ratio M/F, 2.1) satisfied the criteria for severe malaria. On admission, the following signs and symptoms were observed in more than one-fourth of the patients: fever (98%), impairment of consciousness (81.8%), multiple convulsions (70.7%), cardiovascular collapse (61.6%), respiratory distress (43.4%), severe anaemia ≤ 80 g/L (36.4%), haemoglobinuria (27.3%), and renal failure (25.3%). Patients were treated with parenteral quinine or artemether. Fourteen (14.1%) patients died. Multiple convulsions, respiratory distress, severe anaemia, haemoglobinuria, acute renal failure, jaundice, and abnormal bleeding occurred more frequently (p < 0.05) in deceased patients. Mortality due to severe falciparum malaria is high among adults in southern Mauritania. An adoption of the WHO-recommended first-line treatment for severe malaria, such as parenteral artesunate, is required to lower the mortality rate associated with severe malaria.

scholarly journals PO 8271 PFHRP2 GENE DELETIONS IN PLASMODIUM FALCIPARUM AND SCHISTOSOMA MANSONI CO-INFECTIONS: AN EMERGING CHALLENGE FOR MALARIA RAPID DIAGNOSTIC TESTS

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A25.2-A25
Author(s):  
Hilda Echelibe ◽  
Masumbe Netongo Palmer ◽  
Nji Akindeh ◽  
Wilfred Mbacham
Keyword(s):  
Plasmodium Falciparum ◽  
Schistosoma Mansoni ◽  
Diagnostic Tests ◽  
False Negative ◽  
Rapid Diagnostic Tests ◽  
Sub Saharan Africa ◽  
P Value ◽  
Gene Deletions ◽  
Malaria Rdts ◽  
Malaria Rapid Diagnostic Tests

BackgroundMalaria and schistosomiasis are infections that have a great impact in sub-Saharan Africa based on their high morbidity and mortality rates. We suggest the possibility that the microenvironment created from interactions between the parasites involved generates a pressure on the malaria parasite which could in turn favour the parasite’s adaptation or escape through Pfhrp2 gene deletions. Thus, this study aimed at determining the association between the co-infection with both parasites and false-negative PfHRP2-based malaria rapid diagnostic tests which occur because of these deletions.MethodsThis pilot study was conducted in a total of 149 children aged 7–17 years living in Yorro, located in the Mbam-Inoubou division of the Center region of Cameroon. We collected fresh stool samples from each participant to identify Schistosoma mansoni (Sm) eggs by Kato Katz method and blood samples to identify the ring stages of Plasmodium falciparum (Pf) by thick smear. Malaria rapid diagnostic test and Pfhrp2 gene polymerase chain reaction were performed. The association between the co-infection with Sm/Pf and the false-negative malaria RDTs was determined by the Fisher’s exact test. A p value<0.05 was considered statistically significant.ResultsOur results showed that samples were singly infected with Sm, Pf, co-infected (Sm/Pf) and negative for both infections at frequencies of 12%, 43%, 30.2% and 14.8% respectively. False-negative PfHRP2-based RDTs were observed in 4.7% of the participants. A higher frequency (5/7) of the cases with false-negative malaria RDTs were co-infected with Sm/Pf. A p value of 0.027 showed statistical significance in the association of Sm/Pf co-infection and false-negative PfHRP2-based RDTs.ConclusionA significant association of Plasmodium falciparum and Schistosoma mansoni co-infection with false-negative PfHRP2-based RDTs supports the case for a plausible implication of Pfhrp2 gene deletions, with consequences for malaria rapid diagnostic testing.

scholarly journals Update on field use of the available drugs for the chemotherapy of human African trypanosomiasis

Parasitology ◽  
2012 ◽  
Vol 139 (7) ◽  
pp. 842-846 ◽  
Author(s):  
P. P. SIMARRO ◽  
J. FRANCO ◽  
A. DIARRA ◽  
J. A. RUIZ POSTIGO ◽  
J. JANNIN
Keyword(s):  
Human African Trypanosomiasis ◽  
Treatment Time ◽  
Financial Burden ◽  
World Health ◽  
African Trypanosomiasis ◽  
Patient Cost ◽  
Drug Of Choice ◽  
Control Programmes ◽  
Health Organization ◽  
The Cost

SUMMARYDespite the fact that eflornithine was considered as the safer drug to treat human African trypanosomiasis (HAT) and has been freely available since 2001, the difficulties in logistics and cost burden associated with this drug meant that the toxic melarsoprol remained the drug of choice. The World Health Organization responded to the situation by designing a medical kit containing all the materials needed to use eflornithine, and by implementing a training and drugs distribution programme which has allowed a transition to this much safer treatment. The introduction of the combination of nifurtimox and eflornithine (NECT) has accelerated the shift from melarsoprol to the best treatment available, due to reduced dosage and treatment time for eflornithine that has significantly lessened the cost and improved the burden of logistics encountered during treatment and distribution. The decrease in the use of more dangerous but cheaper melarsoprol has meant a rise in the per patient cost of treating HAT. Although NECT is cheaper than eflornithine monotherapy, an unexpected consequence has been a continuing rise in the per patient cost of treating HAT. The ethical decision of shifting to the best available treatment imposes a financial burden on HAT control programmes that might render long-term application unsustainable. These factors call for continuing research to provide new safer and more effective drugs that are simple to administer and cheaper when compared to current drugs.

scholarly journals The Role of Antigen Rapid Diagnostic Test in COVID-19 Diagnosis

2021 ◽  
Vol 1 (1) ◽  
pp. 108-111
Author(s):  
Ronni Mol Joji ◽  
Mohammad Shahid
Keyword(s):  
Diagnostic Tests ◽  
Point Of Care ◽  
Rapid Diagnostic Tests ◽  
World Health ◽  
Complementary Role ◽  
Reverse Transcription Quantitative Pcr ◽  
Highly Sensitive ◽  
Health Organization ◽  
Random Screening

Since the emergence of a novel infection due to the SARS-CoV-2 virus (COVID-19), the World Health Organization has urged countries to develop diagnostic tests to combat the pandemic. Molecular assays were developed following the release of the gene sequence of the virus in January 2020. Reverse transcription-quantitative PCR (RT-qPCR) is taken as the gold standard for the diagnosis of COVID-19. However, due to its limitations, highly sensitive methods for detecting antigens (antigen rapid diagnostic tests) have been developed that would help in a timely and accurate diagnosis. Antigen rapid diagnostic tests (Ag-RDTs) can help guide patient management at the point of care by random screening, re-testing, and timely decision-making in the field of public health. When the affordability and validity of the diagnostic assay are involved, no assay can show 100% correct results. Further studies need to be done to better understand the response of the Ag-RDTs in different settings. Nevertheless, Ag-RDTs can play a complementary role in the response and case management of COVID-19.

scholarly journals An atypical case: RT-PCR-negative, sero-positive covid-19 patient

Pneumologia ◽  
2020 ◽  
Vol 69 (2) ◽  
pp. 107-114
Author(s):  
William Suriady ◽  
Andika Chandra Putra ◽  
Wiwien Heru Wiyono ◽  
Mohammad Fahmi Alatas ◽  
Bettia Bermawi ◽  
...  
Keyword(s):  
False Negative ◽  
Severe Pneumonia ◽  
World Health ◽  
Diagnostic Process ◽  
The Novel ◽  
Rt Pcr ◽  
Atypical Case ◽  
Polymerase Chain ◽  
Novel Coronavirus ◽  
Health Organization

Abstract The novel coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has become a public health emergency of international concern. The first confirmed COVID-19 case in Indonesia was announced on 2 March 2020, and later on, 11,192 confirmed cases were reported as of 3 May. The World Health Organization has stated that performing a real-time reverse transcription–polymerase chain reaction (RT-PCR) specific for SARS-CoV-2 on specimens from the upper and the lower respiratory tracts, especially nasopharyngeal and oropharyngeal swabs, is the standard diagnostic procedure for COVID-19. In Indonesia, we also use other diagnostic tests, such as rapid antibody tests specific for SARS-CoV-2. Herein, we report an atypical case of COVID-19 and describe the diagnostic process, the clinical course, with progression to severe pneumonia on Week 3 of illness and the case management. We also try to highlight the possibility of false-negative RT-PCR tests.

scholarly journals Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium falciparum Malaria in Bohicon and Kandi, Republic of Benin, 2018–2019

2021 ◽  
Author(s):  
Augustin Kpemasse ◽  
Fortune Dagnon ◽  
Ramani Saliou ◽  
Alexis Sacca Yarou Maye ◽  
Cyriaque Dossou Affoukou ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Falciparum Malaria ◽  
World Health ◽  
Antimalarial Resistance ◽  
Resistance Markers ◽  
Republic Of Benin ◽  
Health Organization ◽  
Treatment Policies ◽  
Parasitological Response ◽  
C580y Mutation

In 2005, artemether-lumefantrine (AL), an artemisinin-based combination therapy, was introduced as the first-line treatment of uncomplicated Plasmodium falciparum malaria in Benin. Per World Health Organization recommendations to monitor the efficacy of antimalarial treatment, we conducted a therapeutic efficacy study with AL for uncomplicated P. falciparum malaria in Bohicon and Kandi, Benin, from 2018 to 2019. Febrile patients aged 6 to 59 months with confirmed P. falciparum monoinfection received supervised doses of AL for 3 days. We monitored patients clinically and parasitologically on days 1, 2, 3, 7, 14, 21, and 28. A molecular analysis to detect mutations in the P. falciparum Kelch propeller gene (Pfk13) gene was carried out on day 0 samples. A total of 205 patients were included in the study. In Bohicon, the uncorrected adequate clinical and parasitological response (ACPR) proportion was 91.3% (95% confidence interval [CI]: 84.6–95.8%), whereas in Kandi this proportion was 96.7% (95% CI: 90.6–99.3%). Genotype-corrected ACPR proportions were 96.3% (95% CI: 90.9–99.0%) and 96.7% (95% CI: 90.6–99.3%) in Bohicon and Kandi, respectively. On day 3, 100% of patients in Bohicon and 98.9% of patients in Kandi had undetectable parasitemia. The C580Y mutation in the Pfk13 gene was not observed. AL remains effective for P. falciparum malaria in these two sites in Benin. Monitoring antimalarial efficacy and prevalence of molecular-resistance markers in Benin should be continued to allow for early detection of antimalarial resistance and to guide treatment policies.

scholarly journals Xpert MTB/RIF Ultra is highly sensitive for the diagnosis of tuberculosis lymphadenitis in an HIV-endemic setting

2021 ◽  
Author(s):  
Stephanie Minnies ◽  
Byron W.P. Reeve ◽  
Loren Rockman ◽  
Georgina Nyawo ◽  
Charissa C. Naidoo ◽  
...  
Keyword(s):  
Clinical Investigation ◽  
False Negative ◽  
Needle Aspiration ◽  
World Health ◽  
Number Of Patients ◽  
Highly Sensitive ◽  
Specimen Processing ◽  
Increased Sensitivity ◽  
Health Organization ◽  
Low Sensitivity

Background: Tuberculosis lymphadenitis (TBL) is the most common extrapulmonary TB (EPTB) manifestation. Xpert MTB/RIF Ultra (Ultra) is a World Health Organization-endorsed diagnostic test, but performance data for TBL, including on non-invasive specimens, are limited. Methods: Fine needle aspiration biopsies (FNABs) from outpatients (≥18 years) with presumptive TBL (n=135) underwent: 1) routine Xpert (later Ultra once programmatically available), 2) a MGIT 960 culture (if Xpert- or Ultra-negative, or rifampicin-resistant), and 3) study Ultra. Concentrated paired urine underwent Ultra. Primary analyses used a microbiological reference standard (MRS). Results: In a head-to-head comparison (n=92) of FNAB study Ultra and Xpert, Ultra had increased sensitivity [91% (95% confidence interval 79, 98) vs. 72% (57, 84); p=0.016] and decreased specificity [76% (61, 87) vs. 93% (82, 99); p=0.020], and detected patients not on treatment. HIV nor alternative reference standards affected sensitivity and specificity. In patients with both routine and study Ultras, the latter detected more cases [+20% (0, 42); p=0.034] and, further indicative of potential laboratory-based room-for-improvement (e.g., specimen processing optimisation), false-negative study Ultras were more inhibited than true-positives. Study Ultra false-positives had less mycobacterial DNA than true-positives [trace-positive proportions 59% (13/22) vs. 12% (5/51); p<0.001]. “Trace” exclusion or recategorization removed potential benefits offered over Xpert. Urine Ultra had low sensitivity [18% (7, 35)]. Conclusions: Ultra on FNABs is highly sensitive and detects more TBL than Xpert. Patients with FNAB Ultra-positive “trace” results, most of whom will be culture-negative, may require additional clinical investigation. Urine Ultra could reduce the number of patients needing invasive sampling.

scholarly journals A geo-coded inventory of anophelines in the Afrotropical Region south of the Sahara: 1898-2016

2017 ◽  
Vol 2 ◽  
pp. 57 ◽  
Author(s):  
David Kyalo ◽  
Punam Amratia ◽  
Clara W. Mundia ◽  
Charles M. Mbogo ◽  
Maureen Coetzee ◽  
...  
Keyword(s):  
Malaria Control ◽  
Sub Saharan Africa ◽  
World Health ◽  
Reference Source ◽  
Vector Species ◽  
Control Programmes ◽  
Sub Saharan ◽  
Formed Part ◽  
The 1960S ◽  
Health Organization

Background: Understanding the distribution of anopheline vectors of malaria is an important prelude to the design of national malaria control and elimination programmes. A single, geo-coded continental inventory of anophelines using all available published and unpublished data has not been undertaken since the 1960s. Methods: We have searched African, European and World Health Organization archives to identify unpublished reports on anopheline surveys in 48 sub-Saharan Africa countries. This search was supplemented by identification of reports that formed part of post-graduate theses, conference abstracts, regional insecticide resistance databases and more traditional bibliographic searches of peer-reviewed literature. Finally, a check was made against two recent repositories of dominant malaria vector species locations (circa 2,500). Each report was used to extract information on the survey dates, village locations (geo-coded to provide a longitude and latitude), sampling methods, species identification methods and all anopheline species found present during the survey. Survey records were collapsed to a single site over time.    Results: The search strategy took years and resulted in 13,331 unique, geo-coded survey locations of anopheline vector occurrence between 1898 and 2016. A total of 12,204 (92%) sites reported the presence of 10 dominant vector species/sibling species; 4,473 (37%) of these sites were sampled since 2005. 4,442 (33%) sites reported at least one of 13 possible secondary vector species; 1,107 (25%) of these sites were sampled since 2005. Distributions of dominant and secondary vectors conform to previous descriptions of the ecological ranges of these vectors. Conclusion: We have assembled the largest ever geo-coded database of anophelines in Africa, representing a legacy dataset for future updating and identification of knowledge gaps at national levels. The geo-coded database is available on Harvard Dataverse as a reference source for African national malaria control programmes planning their future control and elimination strategies.

scholarly journals False negative HIV antibody test in HIV infected children who receive early antiretroviral treatment in a resource-limited setting

2012 ◽  
Vol 4 (1) ◽  
pp. 6 ◽  
Author(s):  
Gerardo Alvarez-Uria ◽  
Praveen K. Naik ◽  
Manoranjan Midde ◽  
Shanmugamari Kannan ◽  
Raghuprakash Reddy
Keyword(s):  
False Negative ◽  
Rapid Test ◽  
Antibody Test ◽  
Rural Setting ◽  
World Health ◽  
Enzyme Linked Immunosorbent Assay ◽  
Resource Limited ◽  
One Year ◽  
Health Organization ◽  
Early Antiretroviral Treatment

<p>With the implementation of 2010 World Health Organization guidelines, the number of infants from developing countries who will initiate antiretroviral therapy (ART) will increase considerably. In this study we describe the HIV antibody tests of 14 HIV infected children who initiated ART at age less than one year in a rural setting of India. The HIV rapid test was negative in seven and indeterminate in two cases, whereas the HIV enzyme-linked immunosorbent assay (ELISA) antibody test was negative in three and indeterminate in one case. In one child who had both negative HIV rapid test and ELISA initially, HIV serology turned positive after having a virological failure to ART, suggesting the possibility of utilizing HIV serology for monitoring ART effectiveness in children who experience HIV seroreversion. In conclusion, HIV seroreversion of children with early initiation of ART is common and should be considered for avoiding misdiagnosis of HIV infection.</p><p> </p>

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