Progress on the development of rapid diagnostic tests for foodborne neglected zoonotic helminthiases : a systematic review

Background: Foodborne Neglected Zoonotic Helminths (FNZH) are parasites of both economic and public health importance. They include Taenia solium, Echinococcus granulosus sensu lato, Echinococcus multilocularis and Foodborne trematodes (FBT). FNZH are earmarked for major interventions for control, elimination and eradication. This systematic review highlights the progress towards development of rapid tests for the diagnosis of FNZH since 2010 when they were listed as neglected tropical diseases. Methodology: A systematic search was conducted in three databases, World of Science, Embase and PubMed using the same search phrase. The search produced 480 hits. Three studies from back referencing were included. Only 22 of these met the inclusion criteria. Data was extracted from these and presented qualitatively. Results: Twenty-five rapid diagnostic tests were found to have been developed since 2010, eight for diagnosis of T. solium infections, eight for echinococcosis and nine for FBT infections. The rapid tests for diagnosing T. solium infections included six antibody detecting and two antigen detecting tests. They constitute a combination among them, with some tests providing qualitative, others quantitative results. Similarly, seven out of the eight rapid tests developed for Echinococcus infections were antibody detecting tests save for one loop mediated isothermal amplification test. All of them were qualitative tests. For FBT infections, nine rapid tests were described; two antibody and one nucleic acid detecting test for diagnosis of Fascioliasis; three nucleic acid detecting tests for Opisthorchiasis; one antibody detecting test for Paragonimiasis; and for Clonorchiasis, one antibody and one nucleic acid detecting test. The FBT infection rapid tests were all qualitative in nature. Most of these tests have not undergone field evaluation in endemic areas where they will be used most. Conclusion: This review describes the development and evaluation of rapid diagnostic tests, while highlighting the need for in depth validations of the tools to determine how well they can perform in endemic areas

Malaria Antifolate Resistance With Contrasting Plasmodium Falciparum Dihydrofolate Reductase (DHFR) Polymorphisms in Humans and Anopheles Mosquitoes

Surveillance for drug-resistant parasites in human blood is a major effort in malaria control. Here we report contrasting antifolate resistance polymorphisms in Plasmodium falciparum when parasites in human blood were compared with parasites in Anopheles vector mosquitoes from sleeping huts in rural Zambia. DNA encoding P. falciparum dihydrofolate reductase (EC 1.5.1.3) was amplified by PCR with allele-specific restriction enzyme digestions. Markedly prevalent pyrimethamine-resistant mutants were evident in human P. falciparum infections - S108N (\u3e90%), with N51I, C59R, and 108N+51I+59R triple mutants (30-80%). This resistance level may be from selection pressure due to decades of sulfadoxine/pyrimethamine use in the region. In contrast, cycloguanil-resistant mutants were detected in very low frequency in parasites from human blood samples - S108T (13%), with A16V and 108T+16V double mutants (∼4%). Surprisingly, pyrimethamine-resistant mutants were of very low prevalence (2-12%) in the midguts of Anopheles arabiensis vector mosquitoes, but cycloguanil-resistant mutants were highly prevalent - S108T (90%), with A16V and the 108T+16V double mutant (49-57%). Structural analysis of the dihydrofolate reductase by in silico modeling revealed a key difference in the enzyme within the NADPH binding pocket, predicting the S108N enzyme to have reduced stability but the S108T enzyme to have increased stability. We conclude that P. falciparum can bear highly host-specific drug-resistant polymorphisms, most likely reflecting different selective pressures found in humans and mosquitoes. Thus, it may be useful to sample both human and mosquito vector infections to accurately ascertain the epidemiological status of drug-resistant alleles

Prescribing Patterns of Antibiotics According to the WHO AWaRe Classification during the COVID-19 Pandemic at a Teaching Hospital in Lusaka, Zambia: Implications for Strengthening of Antimicrobial Stewardship Programmes

Irrational and inappropriate prescribing of antibiotics is a major problem that can lead to the development of antimicrobial resistance (AMR). In Zambia, there is insufficient information on the prescribing patterns of antibiotics according to the World Health Organization (WHO) AWaRe classification. Therefore, this study assessed the prescribing patterns of antibiotics using the AWaRe classification during the COVID-19 pandemic at the University Teaching Hospital in Lusaka, Zambia. A cross-sectional study was conducted using 384 patient medical files at the University Teaching Hospital in Lusaka, Zambia, from August 2022 to September 2022. All antibiotics were classified according to the WHO “AWaRe” tool and assessed for appropriateness using the 2020 Zambian Standard Treatment Guidelines. Of the 384 patient medical files reviewed, antibiotics were prescribed 443 times. The most prescribed antibiotics were ceftriaxone (26.6%), metronidazole (22.6%), amoxicillin (10.4%), amoxicillin/clavulanic acid (5.6%), and azithromycin (5%). The prescribing of 42.1% of “Watch” group antibiotics was greater than the recommended threshold by the WHO. Most antibiotics were prescribed for respiratory infections (26.3%) and gastrointestinal tract infections (16.4%). The most prescribed antibiotic was ceftriaxone, a Watch antibiotic. This is a worrisome observation and calls for strengthened antimicrobial stewardship and implementation of the AWaRe framework in prescribing antibiotics

Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS)

Rationale: Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome (ARDS). Causality of these associations has never been demonstrated. Objectives: To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity. Methods: Human, murine and in vitro primary alveolar epithelial cell work were included in this study. Findings: Vitamin D deficiency (plasma 25(OH)D levels 600 genes. In a clinical setting, pharmacological repletion of vitamin D prior to oesophagectomy reduced the observed changes of in vivo measurements of alveolar capillary damage seen in deficient patients. Conclusions: Vitamin D deficiency is common in people who develop ARDS. This deficiency of vitamin D appears to contribute to the development of the condition, and approaches to correct vitamin D deficiency in patients at risk of ARDS should be developed

Detection of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli in Market-Ready Chickens in Zambia

The frequent administering of antibiotics in the treatment of poultry diseases may contribute to emergence of antimicrobialresistant strains. The objective of this study was to detect the presence of extended-spectrum β-lactamase- (ESBL-) producing Escherichia coli in poultry in Zambia. A total of 384 poultry samples were collected and analyzed for ESBL-producing Escherichia coli.The cultured E. coli isolates were subjected to antimicrobial susceptibility tests and the polymerase chain reaction for detection of bla CTX-M, bla SHV, and bla TEM genes. Overall 20.1%, 77/384, (95% CI; 43.2?65.5%) of total samples analyzed contained ESBLproducing Escherichia coli. The antimicrobial sensitivity test revealed that 85.7% (66/77; CI: 75.7?92) of ESBL-producing E. coli isolates conferred resistance to beta-lactamand other antimicrobial agents.These results indicate that poultry is a potential reservoir for ESBL-producing Escherichia coli.The presence of ESBL-producing Escherichia coli in poultry destined for human consumption requires strengthening of the antibiotic administering policy. This is important as antibiotic administration in food animals is gaining momentum for improved animal productivity in developing countries such as Zambia

Operational characteristics of an antibody detecting point of care test for Taenia solium infections in a community and hospital setting

BACKGROUND: Diagnostic test evaluation includes measures of performance and assessment of operational characteristics. The latter focuses on end-user understanding of instructions to perform the test, ease of use, test turnaround time and ease of result interpretation. This study aimed to assess user comprehension of training for and ease of use of a Taenia solium point of care test (TS POC) evaluated in a community and hospital setting in Zambia and Tanzania, respectively. METHODS: The TS POC is a three-step in-house-produced rapid diagnostic test (RDT) for the simultaneous detection of taeniosis (TST) and cysticercosis (TSCC) antibodies. Data collected by administering questionnaires to 29 end-users and from the main evaluation database was analyzed quantitatively. RESULTS: End-users (28/29, 97%) perceived that the training they received for performing the test was sufficient. They performed 4080 tests, of which 80 were invalid. The community-based study and TST tests had higher invalid rates. The overall result interpretation was within the acceptable range of RDTs with an overall disagreement between readers of 3.3%. The Kappa coefficient of agreement was 85 and 82% for TSCC and TST, respectively. There was more disagreement among readers in the community-based study. CONCLUSION: End-users rated the TS POC kit moderate in terms of ease of use citing long test turnaround time and difficulties in using the blood transfer device. Overall, the operational performance of the TS POC kit and end-users was within the established acceptable performance range. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06320-3

Successful multi-partner response to a cholera outbreak in Lusaka, Zambia 2016: a case control study

Background: A Cholera outbreak was reported in Lusaka District between February and May 2016, with 1,079 cases and 20 deaths recorded in the per-urban areas. Bauleni catchment area alone reported 441 (40.9%) case patients with case fatality rate of 4 (0.9%). Bauleni clinic was one of the three established cholera treatment centres (CTC) and other two being Kanyama and Matero Health Centres. Ministry of Health engaged partners that conducted a multi-intervention response to the outbreak. This study is aimed at identifying factors associated with the outbreak.Materials and methods: We conducted a case-control study, at the ratio 1:3, to identify risk factors associated with cholera outbreak. We identified cases of cholera through the cholera register at Bauleni health centre and randomly selected population based controls being residents of Bauleni Township without watery diarrhoea. The standard case definition for suspected cholera case was any person of any age with profuse, effortless watery diarrhoea (three or more stools in 24 hours), with or without vomiting. Aconfirmed cholera case was defined as any person suspected to have cholera with a positive  laboratory result. Univariate and multivariate analysis was performed using Epi-Info version 3.5.4 and Stata version 11.2.Results: On the Cholera Treatment Centre surveillance case-patients register, out of 441 cases, 241 (54.6%) cases were male while 200 (45.4 %%) cases were female, with an attack rate of 14.8/1,000 population and 4 (0.9%) fatalities. The study participants, who included 49 casepatients and 151 controls, had mean-age of 31 years [range, 29-34 years]. Positive Vibrio in stool cholera was associated with drinking inadequately treated borehole water [Adjusted OR=0.79; 95% CI (0.10-6.04), p>0.05]. This odds ratio was adjusted for level education and gender to control and account for any confounding. Though this finding was not statistically significant at p>0.05, the laboratory result was biologically significant as vibrio cholerae was isolated in the borehole water. Drinking treated water was protective [Adjusted OR 0.13; 95% CI (0.05-0.31, p<0.05].Conclusion: Improving methods that promote safe drinking water are likely to be effective measures in averting future cholera outbreaks in this setting.Keywords: Cholera, Lusaka, risk factors, case contro

Operational characteristics of an antibody detecting point of care test for Taenia solium infections in a community and hospital setting

Background Diagnostic test evaluation includes measures of performance and assessment of operational characteristics. The latter focuses on end-user understanding of instructions to perform the test, ease of use, test turnaround time and ease of result interpretation. This study aimed to assess user comprehension of training for and ease of use of a Taenia solium point of care test (TS POC) evaluated in a community and hospital setting in Zambia and Tanzania, respectively. Methods The TS POC is a three-step in-house-produced rapid diagnostic test (RDT) for the simultaneous detection of taeniosis (TST) and cysticercosis (TSCC) antibodies. Data collected by administering questionnaires to 29 end-users and from the main evaluation database was analyzed quantitatively. Results End-users (28/29, 97%) perceived that the training they received for performing the test was sufficient. They performed 4080 tests, of which 80 were invalid. The community-based study and TST tests had higher invalid rates. The overall result interpretation was within the acceptable range of RDTs with an overall disagreement between readers of 3.3%. The Kappa coefficient of agreement was 85 and 82% for TSCC and TST, respectively. There was more disagreement among readers in the community-based study. Conclusion End-users rated the TS POC kit moderate in terms of ease of use citing long test turnaround time and difficulties in using the blood transfer device. Overall, the operational performance of the TS POC kit and end-users was within the established acceptable performance range

The epidemiology of human Taenia solium infections: A systematic review of the distribution in Eastern and Southern Africa.

BackgroundTaenia solium is a tapeworm that causes taeniosis in humans and cysticercosis in humans and pigs. Within Eastern and Southern Africa (ESA), information on the presence of human taeniosis and cysticercosis seems scarce. This systematic review aimed to describe the current information available and gaps in the epidemiology of human T. solium infections in ESA.Methods/principle findingsScientific literature published between 1st January 2000 and 20th June 2022 in international databases [MEDLINE (Ovid), Embase (Ovid), Global Health (Ovid), Scopus (Elsevier), African Index Medicus (via WHO Global Index Medicus), and Open Grey] was systematically reviewed for ESA. The study area included 27 countries that make up the ESA region. Information on either taeniosis, cysticercosis or NCC was available for 16 of 27 countries within the region and a total of 113 reports were retained for the review. Most case reports for cysticercosis and NCC were from South Africa, while Tanzania had the most aggregated cysticercosis reports. Eleven countries reported on NCC with seven countries reporting data on NCC and epilepsy. Unconfirmed human T. solium taeniosis cases were reported in nine countries while two countries (Madagascar and Zambia) reported confirmed T. solium cases. The cysticercosis seroprevalence ranged between 0.7-40.8% on antigen (Ag) ELISA and between 13.1-45.3% on antibody (Ab) ELISA. Based on immunoblot tests the Ab seroprevalence was between 1.7-39.3%, while the proportion of NCC-suggestive lesions on brain CT scans was between 1.0-76% depending on the study population. The human taeniosis prevalence based on microscopy ranged between 0.1-14.7%. Based on Copro Ag-ELISA studies conducted in Kenya, Rwanda, Tanzania, and Zambia, the highest prevalence of 19.7% was reported in Kenya.ConclusionsDespite the public health and economic impact of T. solium in ESA, there are still large gaps in knowledge about the occurrence of the parasite, and the resulting One Health disease complex, and monitoring of T. solium taeniosis and cysticercosis is mostly not in place