Background Clinical and laboratory diagnosis of cutaneous leishmaniasis (CL) is hampered by under-ascertainment of direct microscopy. Methods This study compared the diagnostic accuracy of qPCR on ...DNA extracted from filter paper to the accuracy of direct smear slide microscopy in participants presenting with a cutaneous lesion suspected of leishmaniasis to 16 rural healthcare centers in the Ecuadorian Amazon and Pacific regions, from January 2019 to June 2021. We used Bayesian latent class analysis to estimate test sensitivity, specificity, likelihood ratios (LR), and predictive values (PV) with their 95% credible intervals (95%CrI). The impact of sociodemographic and clinical characteristics on predictive values was assessed as a secondary objective. Results Of 320 initially included participants, paired valid test results were available and included in the diagnostic accuracy analysis for 129 from the Amazon and 185 from the Pacific region. We estimated sensitivity of 68% (95%CrI 49% to 82%) and 73% (95%CrI 73% to 83%) for qPCR, and 51% (95%CrI 36% to 66%) and 76% (95%CrI 65% to 86%) for microscopy in the Amazon and Pacific region, respectively. In the Amazon, with an estimated disease prevalence among participants of 73%, negative PV for qPCR was 54% (95%CrI 5% to 77%) and 44% (95%CrI 4% to 65%) for microscopy. In the Pacific, (prevalence 88%) the negative PV was 34% (95%CrI 3% to 58%) and 37% (95%CrI 3% to 63%). The addition of qPCR parallel to microscopy in the Amazon increases the observed prevalence from 38% to 64% (+26 (95%CrI 19 to 34) percentage points). Conclusion The accuracy of either qPCR on DNA extracted from filter paper or microscopy for CL diagnosis as a stand-alone test seems to be unsatisfactory and region-dependent. We recommend further studies to confirm the clinically relevant increment found in the diagnostic yield due to the addition of qPCR.
Abstract
Background
Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is an important malaria control strategy in sub-Saharan Africa. Indeed, it overcomes the ...risk of misdiagnosis due to low peripheral parasitemia during pregnancy by treating women with SP on predetermined schedules. However, over time, the spread of
Plasmodium
-resistant strains has threatened this strategy in many countries. As an alternative, the intermittent screening and treatment for pregnancy (ISTp) aims at a monthly screening of pregnant women, preferably by using very sensitive tests such as ultrasensitive rapid diagnostic tests (us-RDTs) and the treatment of positive cases with artemisinin-based combination therapy (ACT) regardless of the presence of symptoms. Unlike IPTp-SP, ISTp prevents overuse of antimalarials limiting the drug pressure on parasites, an advantage which can be potentiated by using an ACT like pyronaridine-artesunate (Pyramax®) that is not yet used in pregnant women in the field.
Methods
This study aims to compare the non-inferiority of ISTp using us-RDTs and Pyramax® versus IPTp-SP on malaria in pregnancy through a randomized clinical trial performed in Kisenso, Kinshasa, the Democratic Republic of the Congo, a malaria perennial transmission area.
Discussion
The results will be essential for the National Malaria Control Program to update the malaria prevention policy in pregnant women in the Democratic Republic of the Congo.
Trial registration
ClinicalTrials.gov NCT04783051
Febrile illnesses are among the most important reasons for medical consultation in sub-Saharan Africa and are frequently treated with antimicrobials due to the unavailability of appropriate ...diagnostic tools. This practice leads to antimicrobial resistance, with increasing mortality and morbidity as result. One of the few accessible diagnostic tools available in low resource settings is malaria rapid diagnostic tests (mRDTs) which contributed to reducing the over-prescription of anti-malarials, but cannot guide antibiotic prescriptions. To circumvent this problem, we explored whether combined testing with mRDT and c-reactive protein (CRP) could improve the diagnosis of febrile illnesses and subsequent prescription of antibiotics.
Clinical specimens (blood, stool and urine) collected from 396 febrile children (axillary temperature of ≥ 37.5 °C) were analyzed with rapid diagnostic tests (malaria and CRP) and microbiology culture to establish the possible cause of fever. Actual antimicrobial prescriptions given to the children were compared with those that could be given based on combined CRP-malaria testing.
In total, 68.7% (272/396) of malaria cases were diagnosed by mRDT-Pf-HRP-2. CRP test was positive in 84.3% (334/396) of the children, but bacterial infections were confirmed in 12.4% (49/396) of them. A possible cause of fever could not be established in 20.5% (81/396) of cases. Based on the diagnostic practice in place, 265 of the children with a positive mRDT-Pf-HRP-2 received anti-malarial treatment. Furthermore, 89.5% (111/124) of negative mRDT results received antibiotic treatment and 37.1% (46/124) received antimalarial treatment. Of these 124 cases, 80 had positive CRP tests and 44 negative CRP tests. If the results of CRP testing are considered, 44 CRP/mRDT negative children would not get antibiotic treatment, resulting in a 35.5% reduction in antibiotic prescriptions. However, 2 cases with a bacterial infection would be denied appropriate treatment.
Combining mRDT-PfHRP2 with CRP testing is particularly useful in children for whom both tests are negative as it results in a reduction of antibiotics prescriptions. However, there is a risk to miss potential severe bacterial infections and a close follow-up of these cases is strongly recommended.
Abstract
Background
Malaria and dengue fever are the leading causes of acute, undifferentiated febrile illness. In Africa, misdiagnosis of dengue fever as malaria is a common scenario. Through a ...systematic review of the published literature, this study seeks to estimate the prevalence of dengue and malaria coinfection among acute undifferentiated febrile diseases in Africa.
Methods
Relevant publications were systematically searched in the PubMed, Cochrane Library, and Google Scholar until May 19, 2023. A random-effects meta-analysis and meta-regression were used to summarize and examine the prevalence estimates.
Results
Twenty-two studies with 22,803 acute undifferentiated febrile patients from 10 countries in Africa were included. The meta-analysis findings revealed a pooled prevalence of malaria and dengue coinfection of 4.2%, with Central Africa having the highest rate (4.7%), followed by East Africa (2.7%) and West Africa (1.6%). Continent-wide,
Plasmodium falciparum
and acute dengue virus coinfection prevalence increased significantly from 0.9% during 2008–2013 to 3.8% during 2014–2017 and to 5.5% during 2018–2021 (p = 0.0414).
Conclusion
There was a high and increasing prevalence of malaria and acute dengue virus coinfection in Africa. Healthcare workers should bear in mind the possibility of dengue infection as a differential diagnosis for acute febrile illness, as well as the possibility of coexisting malaria and dengue in endemic areas. In addition, high-quality multicentre studies are required to verify the above conclusions.
Protocol registration number
: CRD42022311301.
The World Health Organization has proposed that onchocerciasis elimination (interruption) of transmission be verified in 12 (approximately a third) endemic countries by 2030. The strategy to reach ...this goal is based on ivermectin Mass Drug Administration (MDA) with high geographical and therapeutic coverage. In addition to coverage, high levels of treatment adherence are paramount. We investigated factors associated with ivermectin intake in an area of Ghana with persistent Onchocerca volvulus infection. In August 2021, a cross-sectional mixed-methods study was conducted in 13 onchocerciasis-endemic communities in the Bono Region of Ghana. Individuals aged greater than or equal to 10 years were invited to participate in a questionnaire survey. A total of 48 focus group discussions and in-depth interviews with 10 community drug distributors and 13 community leaders were conducted. A total of 510 people participated in the study median age: 32, interquartile range 30 (20-50) years; 274 (53.7%) were females. Of the total, 320 (62.7%) declared that they adhered to each treatment round and 190 (37.3%) admitted they had not taken ivermectin during at least one MDA round, since becoming eligible for treatment. Of 483 participants with complete information, 139 (28.8%) did not take ivermectin during the last round (March 2021), and 24 (5.0%) had never taken ivermectin (systematic non-adherers). Reasons for not taking ivermectin included previous experience/fear of side-effects, being absent during MDA, pregnancy, the desire to drink alcohol, and drug distribution challenges. Being male, having good knowledge and perception of the disease, and not having secondary or higher level of formal education were significantly associated with higher odds of ivermectin intake. A relatively high level of non-adherence to ivermectin treatment was documented. There is a need for targeted educational and behavioural change campaigns to reverse these trends and ensure a steady course toward meeting onchocerciasis elimination targets in Ghana.
Fever remains a major public health problem. In Burkina Faso, more than half of febrile children are considered not to be infected by malaria. This study prospectively assessed probable (treatable) ...causes of fever in Burkinabe children.
A prospective study was conducted among febrile children (≥37.5 °C) under 5 years of age presenting at four health facilities and one referral hospital in rural Burkina Faso. From each participant, blood was collected for malaria microscopy and culture, urine for dipstick testing and culturing if tested positive for leucocytes and nitrite, stool for rotavirus/adenovirus testing, culture and parasitology, and a nasopharyngeal swab for culture.
In total 684 febrile children were included in the study. Plasmodium falciparum malaria was found in 49.7% (340/684) of the participants and non-malaria infections in 49.1% (336/684) of children. The non-nalaria infections included gastro-intestinal infections (37.0%), common bacterial pathogens of nasopharynx (24.3%), bacterial bloodstream infections (6.0%) and urinary tract infections (1.8%). Nearly 45% (154/340) of the malaria infected children were co-infected with non-nalaria infections, but only 3.2% (11/340) of these co-infections could be considered as a possible alternative cause of fever. In contrast, in the malaria microscopy negative children 18.0% (62/344) of the infections could be the probable cause of the fever. Pathogens were not isolated from 23.7% (162/684) of the febrile cases.
Malaria remains the most common pathogen found in febrile children in Burkina Faso. However, a relative high number of febrile children had non-malaria infections. The correct diagnosis of these non-malaria fevers is a major concern, and there is an urgent need to develop more point-of-care diagnostic tests and capacities to identify and treat the causes of these fevers.
The lack of accurate and feasible diagnostic tests poses a significant challenge to visceral leishmaniasis (VL) healthcare services in endemic areas. To date, various VL diagnostic tests have been or ...are being developed, and their diagnostic performances need to be assessed. In the present study, the diagnostic performances of rk39 RDT, the direct agglutination test (DAT), microscopy, loop-mediated isothermal amplification (LAMP), and miniature direct-on-blood polymerase chain reaction-nucleic acid lateral flow immunoassay (mini-dbPCR-NALFIA) were assessed using quantitative polymerase chain reaction (qPCR) as the reference test in an endemic region of Ethiopia. In this study, 235 suspected VL cases and 104 non-endemic healthy controls (NEHCs) were recruited. Among the suspected VL cases, 144 (61.28%) tested positive with qPCR. The sensitivities for rk39 RDT, DAT, microscopy, LAMP assay, and mini-dbPCR-NALFIA were 88.11%, 96.50%, 76.58%, 94.33%, and 95.80%, respectively. The specificities were 83.33%, 97.96%, 100%, 97.38%, and 98.92% for rk39 RDT, DAT, microscopy, LAMP assay, and mini-dbPCR-NALFIA, respectively. In conclusion, rk39 RDT and microscopy exhibited lower sensitivities, while DAT demonstrated excellent performance. LAMP and mini-dbPCR-NALFIA showed excellent performances with feasibility for implementation in remote endemic areas, although the latter requires further evaluation in such regions.
Many different animal models are in use for drug development for leishmaniasis, but a universal model does not exist. There is a plethora of models, and this review assesses their design, quality, ...and limitations, including the attention paid to animal welfare in the study design and execution. A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines of available literature after the year 2000 describing animal models for leishmaniasis. The risk of bias was determined using the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) risk of bias assessment tool. A total of 10,980 records were initially identified after searching the databases PubMed, EMBASE, LILACS, and SciELO. Based on the application of predetermined exclusion and inclusion criteria, a total of 203 papers describing 216 animal experiments were available for full analysis. Major reasons for exclusion were a lack of essential study information or appropriate ethical review and approval. Mice (82.8%; an average of 35.9 animals per study) and hamsters (17.1%; an average of 7.4 animals per study) were the most frequently used animals, mostly commercially sourced, in the included studies. All studies lacked a formal sample size analysis. The promastigote stages of
or
were most frequently used to establish experimental infections (single inoculum). Animal welfare was poorly addressed in all included studies, as the definition of a human end-point or consideration of the 3Rs (Replacement, Reduction, Refinement) was hardly addressed. Most animals were euthanized at the termination of the experiment. The majority of the studies had an unknown or high risk of bias. Animal experiments for drug development for leishmaniasis mainly poorly designed and of low quality, lack appropriate ethical review, and are deficient in essential information needed to replicate and interpret the study. Importantly, aspects of animal welfare are hardly considered. This underpins the need to better consider and record the details of the study design and animal welfare.
It remains challenging to distinguish malaria from other fever causing infections, as a positive rapid diagnostic test does not always signify a true active malaria infection. This study was designed ...to determine the influence of other causes of fever, prior anti-malarial treatment, and a possible seasonality of the performance of a PfHRP2 RDT for the diagnosis of malaria in children under-5 years of age living in a malaria endemic area.
A prospective etiology study was conducted in 2015 among febrile children under 5 years of age in Burkina Faso. In order to assess the influence of other febrile illnesses, prior treatment and seasonality on the performance of a PfHRP2 RDT in diagnosing malaria, the RDT results were compared with the gold standard (expert microscopic diagnosis of Plasmodium falciparum) and test results were analysed by assuming that prior anti-malarial use and bacterial/viral infection status would have been known prior to testing. To assess bacterial and viral infection status blood, urine and stool samples were analysed.
In total 683 blood samples were analysed with microscopy and RDT-PfHRP2. Plasmodium falciparum malaria was diagnosed in 49.8% (340/683) by microscopy compared to 69.5% (475/683) by RDT-PfHRP2. The RDT-PfHRP2 reported 29.7% (141/475) false positive results and 1.8% (6/340) false negative cases. The RDT-PfHRP2 had a high sensitivity (98.2%) and negative predictive value (97.1%), but a low specificity (58.9%) and positive predictive value (70.3%). Almost 50% of the alternative cause of fever were diagnosed by laboratory testing in the RDT false positive malaria group.
The use of a malaria RDT-PfHRP2 in a malaria endemic area may cause misdiagnosis of the actual cause of fever due to false positive test results. The development of a practical diagnostic tool to screen for other causes of fever in malaria endemic areas is required to save lives.
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