Paracheck-Pf® accuracy and recently treated Plasmodium falciparum infections: is there a risk of over-diagnosis?

BACKGROUND: An assessment of the accuracy of Paracheck Pf, a malaria rapid diagnostic test (RDT) detecting histidine rich protein 2 was undertaken amongst children aged 6-59 months in eastern Democratic Republic of Congo. METHODS: This RDT assessment occurred in conjunction with an ACT efficacy trial. Febrile children were simultaneously screened with both RDT and high quality microscopy and those meeting inclusion criteria were followed for 35 days. RESULTS: 358 febrile children were screened with 180 children recruited for five weeks follow-up. On screening, the RDT accurately diagnosed all 235 true malaria cases, indicating 100% RDT sensitivity. Of the 123 negative slides, the RDT gave 59 false-positive results, indicating 52.0% (64/123) RDT specificity. During follow-up after treatment with an artemisinin-based combination therapy, 98.2% (110/112), 94.6% (106/112), 92.0% (103/112) and 73.5% (50/68) of effectively treated children were still false-positive by RDT at days 14, 21, 28 and 35, respectively. CONCLUSION: Results show that though the use of Paracheck-Pf is as sensitive as microscopy in detecting true malaria cases, a low specificity did present a high frequency of false-positive RDT results. What's more, a duration of RDT false-positivity was found that significantly surpassed the 'fortnight' after effective treatment reported by its manufacturer. Though further research is needed in assessing RDT accuracy, study results showing the presence of frequent false positivity should be taken into consideration to avoid clinicians inappropriately focusing on malaria, not identifying the true cause of illness, and providing unnecessary treatment

Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles

Integrated community case management in a peri-urban setting: a qualitative evaluation in Wakiso District, Uganda.

Integrated community case management (iCCM) strategies aim to reach poor communities by providing timely access to treatment for malaria, pneumonia and diarrhoea for children under 5 years of age. Community health workers, known as Village Health Teams (VHTs) in Uganda, have been shown to be effective in hard-to-reach, underserved areas, but there is little evidence to support iCCM as an appropriate strategy in non-rural contexts. This study aimed to inform future iCCM implementation by exploring caregiver and VHT member perceptions of the value and effectiveness of iCCM in peri-urban settings in Uganda.A qualitative evaluation was conducted in seven villages in Wakiso district, a rapidly urbanising area in central Uganda. Villages were purposively selected, spanning a range of peri-urban settlements experiencing rapid population change. In each village, rapid appraisal activities were undertaken separately with purposively selected caregivers (n = 85) and all iCCM-trained VHT members (n = 14), providing platforms for group discussions. Fifteen key informant interviews were also conducted with community leaders and VHT members. Thematic analysis was based on the 'Health Access Livelihoods Framework'.iCCM was perceived to facilitate timely treatment access and improve child health in peri-urban settings, often supplanting private clinics and traditional healers as first point of care. Relative to other health service providers, caregivers valued VHTs' free, proximal services, caring attitudes, perceived treatment quality, perceived competency and protocol use, and follow-up and referral services. VHT effectiveness was perceived to be restricted by inadequate diagnostics, limited newborn care, drug stockouts and VHT member absence - factors which drove utilisation of alternative providers. Low community engagement in VHT selection, lack of referral transport and poor availability of referral services also diminished perceived effectiveness. The iCCM strategy was widely perceived to result in economic savings and other livelihood benefits.In peri-urban areas, iCCM was perceived as an effective, well-utilised strategy, reflecting both VHT attributes and gaps in existing health services. Depending on health system resources and organisation, iCCM may be a useful transitional service delivery approach. Implementation in peri-urban areas should consider tailored community engagement strategies, adapted selection criteria, and assessment of population density to ensure sufficient coverage

Epidemiology and clinical presentation of the four human parainfluenza virus types

<p>Abstract</p> <p>Background</p> <p>Human parainfluenza viruses (HPIVs) are important causes of upper respiratory tract illness (URTI) and lower respiratory tract illness (LRTI). To analyse epidemiologic and clinical characteristics of the four types of human parainfluenza viruses (HPIVs), patients with acute respiratory tract illness (ARTI) were studied in Guangzhou, southern China.</p> <p>Methods</p> <p>Throat swabs (n=4755) were collected and tested from children and adults with ARTI over a 26-month period, and 4447 of 4755 (93.5%) patients’ clinical presentations were recorded for further analysis.</p> <p>Results</p> <p>Of 4755 patients tested, 178 (3.7%) were positive for HPIV. Ninety-nine (2.1%) samples were positive for HPIV-3, 58 (1.2%) for HPIV-1, 19 (0.4%) for HPIV-2 and 8 (0.2%) for HPIV-4. 160/178 (88.9%) HPIV-positive samples were from paediatric patients younger than 5 years old, but no infant under one month of age was HPIV positive. Seasonal peaks of HPIV-3 and HPIV-1 occurred as autumn turned to winter and summer turned to autumn. HPIV-2 and HPIV-4 were detected less frequently, and their frequency of isolation increased when the frequency of HPIV-3 and HPIV-1 declined. HPIV infection led to a wide spectrum of symptoms, and more “hoarseness” (p=0.015), “abnormal pulmonary breathing sound” (p<0.001), “dyspnoea” (p<0.001), “pneumonia” (p=0.01), and “diarrhoea” (p<0.001) presented in HPIV-positive patients than HPIV-negative patients. 10/10 (100%) HPIV-positive adult patients (≥14 years old) presented with systemic influenza-like symptoms, while 90/164 (54.9%) HPIV-positive paediatric patients (<14 years old) presented with these symptoms (p=0.005). The only significant difference in clinical presentation between HPIV types was “Expectoration” (p<0.001). Co-infections were common, with 33.3%–63.2% of samples positive for the four HPIV types also testing positive for other respiratory pathogens. However, no significant differences were seen in clinical presentation between patients solely infected with HPIV and patients co-infected with HPIV and other respiratory pathogens.</p> <p>Conclusions</p> <p>HPIV infection led to a wide spectrum of symptoms, and similar clinical manifestations were found in the patients with four different types of HPIVs. The study suggested pathogenic activity of HPIV in gastrointestinal illness. The clinical presentation of HPIV infection may differ by patient age.</p