Performance characteristics of loop mediated isothermal amplification (lamp) assay for rapid diagnosis of typhoid infections at city clinics in Nairobi

Abstract

Background Enteric fever continues to be a major public health burden in Kenya as it is in other developing countries. The current diagnostic options are limited with the recent phasing out of the Widal serological test that was unreliable. The gold standard is blood culturing which is also beset with cost and logistical challenges which are common in the typhoid endemic and holo-endemic areas. Due to these diagnosis setbacks, it has been impossible to correctly evaluate the exact burden of typhoid and inform specific mitigation measures at policy and practice levels. Additionally, this has contributed to the prevailing mis-diagnosis and over-diagnosis which are potentially fatal and costly respectively. Objectives Loop isothermal amplification assay (LAMP) is a recently developed technology that is both cost effective, easy to perform, sensitive and specific as shown in previous studies. Furthermore, because using the LAMP method a large amount of DNA is synthesized, simple turbidity can be used to detect the products thus expensive equipment is not necessary in order to give high level of precision. The aim of this study is to test this new technology against the existing options in the diagnosis of typhoid. Methods A cross sectional study will be carried out at city clinics in Nairobi which has a population of approximately 4 million residents with stretched social amenities. Simple random sampling will be done and 160 subjects will be included in the study. Samples will be taken from the subjects and subjected to both blood culture and Loop isothermal amplification assay (LAMP). Laboratory data will be transcript generated by the turbid meter and then entered manually into access database. Data analysis will be done using STATA. Results The LAMP tests had a reasonable agreement with gold standard test. Therefore, laboratories should perform the standard laboratory procedure of LAMP test and follow the standard reporting instead of in ‘reactive’ and ‘non reactive’ terms. The sensitivity, specificity, PPV and NPV of LAMP test were 92.64%, 84.14, 82.89% and 93.24% respectively. Conclusion As typhoid is a highly infectious disease it requires accurate diagnosis so as to enable prompt initiation if therapy and also to reduce the rate of over diagnosis and misdiagnosis. With this novel technology (LAMP), diagnosis of typhoid will be faster and more accurate and can be adopted as the gold standard in detection of typhoid. This study will potentially be the preliminary of a major study on national ‘Typhoid watch