Molecular surveillance reveals the presence of pfhrp2 and pfhrp3 gene deletions in Plasmodium falciparum parasite populations in Uganda, 2017–2019

Abstract Background Histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) are the only RDTs recommended for malaria diagnosis in Uganda. However, the emergence of Plasmodium falciparum histidine rich protein 2 and 3 (pfhrp2 and pfhrp3) gene deletions threatens their usefulness as malaria diagnostic and surveillance tools. The pfhrp2 and pfhrp3 gene deletions surveillance was conducted in P. falciparum parasite populations in Uganda. Methods Three-hundred (n = 300) P. falciparum isolates collected from cross-sectional malaria surveys in symptomatic individuals in 48 districts of eastern and western Uganda were analysed for the presence of pfhrp2 and pfhrp3 genes. Presence of parasite DNA was confirmed by PCR amplification of the 18s rRNA gene, msp1 and msp2 single copy genes. Presence or absence of deletions was confirmed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCR. Results Overall, pfhrp2 and pfhrp3 gene deletions were detected in 29/300 (9.7%, 95% CI 6.6–13.6%) parasite isolates. The pfhrp2 gene was deleted in 10/300 (3.3%, 95% CI 1.6–6.0%) isolates, pfhrp3 in 9/300 (3.0%, 95% CI 1.4–5.6%) while both pfhrp2 and pfhrp3 were deleted in 10/300 (3.3%, 95% CI 1.6–6.0%) parasite isolates. Proportion of pfhrp2/3 deletions was higher in the eastern 14.7% (95% CI 9.7–20.0%) compared to the western region 3.1% (95% CI 0.8–7.7%), p = 0.001. Geographical location was associated with gene deletions aOR 6.25 (2.02–23.55), p = 0.003. Conclusions This is the first large-scale survey reporting the presence of pfhrp2/3 gene deletions in P. falciparum isolates in Uganda. Roll out of RDTs for malaria diagnosis should take into consideration the existence of pfhrp2/3 gene deletions particularly in areas where they were detected. Periodic pfhrp2/3 surveys are recommended to inform future decisions for deployment of alternative RDTs

Uganda's experience in Ebola virus disease outbreak preparedness, 2018-2019.

BACKGROUND: Since the declaration of the 10th Ebola Virus Disease (EVD) outbreak in DRC on 1st Aug 2018, several neighboring countries have been developing and implementing preparedness efforts to prevent EVD cross-border transmission to enable timely detection, investigation, and response in the event of a confirmed EVD outbreak in the country. We describe Uganda's experience in EVD preparedness. RESULTS: On 4 August 2018, the Uganda Ministry of Health (MoH) activated the Public Health Emergency Operations Centre (PHEOC) and the National Task Force (NTF) for public health emergencies to plan, guide, and coordinate EVD preparedness in the country. The NTF selected an Incident Management Team (IMT), constituting a National Rapid Response Team (NRRT) that supported activation of the District Task Forces (DTFs) and District Rapid Response Teams (DRRTs) that jointly assessed levels of preparedness in 30 designated high-risk districts representing category 1 (20 districts) and category 2 (10 districts). The MoH, with technical guidance from the World Health Organisation (WHO), led EVD preparedness activities and worked together with other ministries and partner organisations to enhance community-based surveillance systems, develop and disseminate risk communication messages, engage communities, reinforce EVD screening and infection prevention measures at Points of Entry (PoEs) and in high-risk health facilities, construct and equip EVD isolation and treatment units, and establish coordination and procurement mechanisms. CONCLUSION: As of 31 May 2019, there was no confirmed case of EVD as Uganda has continued to make significant and verifiable progress in EVD preparedness. There is a need to sustain these efforts, not only in EVD preparedness but also across the entire spectrum of a multi-hazard framework. These efforts strengthen country capacity and compel the country to avail resources for preparedness and management of incidents at the source while effectively cutting costs of using a "fire-fighting" approach during public health emergencies

The use of plants in the traditional management of diabetes in Nigeria: Pharmacological and toxicological considerations

Ethnopharmacological relevance: The prevalence of diabetes is on a steady increase worldwide and it is now identified as one of the main threats to human health in the 21st century. In Nigeria, the use of herbal medicine alone or alongside prescription drugs for its management is quite common. We hereby carry out a review of medicinal plants traditionally used for diabetes management in Nigeria. Based on the available evidence on the species׳ pharmacology and safety, we highlight ways in which their therapeutic potential can be properly harnessed for possible integration into the country׳s healthcare system. Materials and methods: Ethnobotanical information was obtained from a literature search of electronic databases such as Google Scholar, Pubmed and Scopus up to 2013 for publications on medicinal plants used in diabetes management, in which the place of use and/or sample collection was identified as Nigeria. ‘Diabetes’ and ‘Nigeria’ were used as keywords for the primary searches; and then ‘Plant name – accepted or synonyms’, ‘Constituents’, ‘Drug interaction’ and/or ‘Toxicity’ for the secondary searches. Results: The hypoglycemic effect of over a hundred out of the 115 plants reviewed in this paper is backed by preclinical experimental evidence, either in vivo or in vitro. One-third of the plants have been studied for their mechanism of action, while isolation of the bioactive constituent(s) has been accomplished for twenty three plants. Some plants showed specific organ toxicity, mostly nephrotoxic or hepatotoxic, with direct effects on the levels of some liver function enzymes. Twenty eight plants have been identified as in vitro modulators of P-glycoprotein and/or one or more of the cytochrome P450 enzymes, while eleven plants altered the levels of phase 2 metabolic enzymes, chiefly glutathione, with the potential to alter the pharmacokinetics of co-administered drugs. Conclusion: This review, therefore, provides a useful resource to enable a thorough assessment of the profile of plants used in diabetes management so as to ensure a more rational use. By anticipating potential toxicities or possible herb–drug interactions, significant risks which would otherwise represent a burden on the country׳s healthcare system can be avoided

A Successful National and Multipartner Approach to Increase Immunization Coverage: The Democratic Republic of Congo Mashako Plan 2018-2020.

BackgroundThe immunization system in the Democratic Republic of the Congo faces many challenges, including persistent large-scale outbreaks of polio, measles, and yellow fever; a large number of unvaccinated children for all antigens; minimal and delayed funding; and poor use of immunization data at all levels. In response, the Expanded Programme on Immunization within the Ministry of Health (MOH) collaborated with global partners to develop a revitalization strategy for the routine immunization (RI) system called the Mashako Plan.Mashako plan design and developmentThe Mashako Plan aimed to increase full immunization coverage in children aged 12-23 months by 15 percentage points overall in 9 of 26 provinces within 18 months of implementation. In 2018, we conducted a diagnostic review and identified gaps in coordination, service delivery, vaccine availability, real-time monitoring, and evaluation as key areas for intervention to improve the RI system. Five interventions were then implemented in the 9 identified provinces.DiscussionAccording to the 2020 vaccine coverage survey, full immunization coverage increased to 56.4%, and Penta3/DTP3 increased to 71.1% across the Mashako Plan provinces; the initial objective of the plan was reached and additional improvements in key service delivery indicators had been achieved. Increases in immunization sessions held per month, national stock of pentavalent vaccine, and supervision visits conducted demonstrate that simple, measurable changes at all levels can quickly improve immunization systems. Despite short-term improvements in all indicators tracked, challenges remain in vaccine availability, regular funding of immunization activities, systematic provision of immunization services, and ensuring long-term sustainability.ConclusionsStrong commitment of MOH staff combined with partner involvement enabled the improvement of the entire system. A simple set of interventions and indicators focused the energy of managers on discrete actions to improve outcomes. Further exploration of the results is necessary to determine the long-term impact and generate all-level engagement for sustainable success in all provinces

Limitations of rapid diagnostic tests in malaria surveys in areas with varied transmission intensity in Uganda 2017-2019: Implications for selection and use of HRP2 RDTs.

BackgroundPlasmodium falciparum histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) are exclusively recommended for malaria diagnosis in Uganda; however, their functionality can be affected by parasite-related factors that have not been investigated in field settings.MethodsUsing a cross-sectional design, we analysed 219 RDT-/microscopy+ and 140 RDT+/microscopy+ dried blood spots obtained from symptomatic children aged 2-10 years from 48 districts in Uganda between 2017 and 2019. We aimed to investigate parasite-related factors contributing to false RDT results by molecular characterization of parasite isolates. ArcGIS software was used to map the geographical distribution of parasites. Statistical analysis was performed using chi-square or Fisher's exact tests, with P ≤ 0.05 indicating significance. Odds ratios (ORs) were used to assess associations, while logistic regression was performed to explore possible factors associated with false RDT results.ResultsThe presence of parasite DNA was confirmed in 92.5% (332/359) of the blood samples. The levels of agreement between the HRP2 RDT and PCR assay results in the (RDT+/microscopy+) and (RDT-/microscopy+) sample subsets were 97.8% (137/140) and 10.9% (24/219), respectively. Factors associated with false-negative RDT results in the (RDT-/microscopy+) samples were parasite density (ConclusionThis is the first evaluation and report of the contributions of pfhrp2/3 gene deletion, non-P. falciparum species, and low-density infections to false-negative RDT results under field conditions in Uganda. In view of these findings, the use of HRP2 RDTs should be reconsidered; possibly, switching to combination RDTs that target alternative antigens, particularly in affected areas, may be beneficial. Future evaluations should consider larger and more representative surveys covering other regions of Uganda

Percent change in volume from expected levels based on prepandemic trends by selected health services across 18 countries, March 2020–February 2021.

Note: The horizontal line at 0% represents the expected volume of services based on prepandemic trends. The gray lines plot country-specific changes in service utilization. The monthly country-specific results are presented in Table A in S1 Text. The red line is a multicountry unweighted moving average of the change in utilization plotted by a locally estimated scatterplot smoothing (LOESS) regression. Details on indicator reporting for each country can be found in Table L in S1 Text. ANC1 refers to First Antenatal Care Visit. ANC4 refers to the Fourth Antenatal Care Visit. BCG refers to bacillus Calmette–Guérin vaccination. OPD refers to Outpatient visits. Penta3 refers to the Third dose of Pentavalent vaccine. PNC1 refers to First Postnatal Care Visit.</p

Expected and additional child, neonatal, and maternal deaths, March 2020 to June 2021.

Expected and additional child, neonatal, and maternal deaths, March 2020 to June 2021.</p