Target product profiles for diagnosis of sepsis: Proposing a new approach for diagnostic innovation

Background & objectives: Sepsis, including neonatal sepsis, remains a prevalent cause of morbidity and mortality in low- and middle-income countries such as India, representing 85 per cent of all sepsis-related deaths globally. Early diagnosis and timely initiation of treatment is challenging due to non-specific clinical manifestations and non-availability of rapid diagnostic tests. There is an urgent need for affordable diagnostics with fast turnaround time catering to the needs of end-users. Target product profiles (TPPs) have been found instrumental in developing ‘fit-for-use’ diagnostics, thus reducing the time taken to facilitate development and improving diagnosis. Hitherto, no such guidance or criteria has been defined for rapid diagnostics for sepsis/neonatal sepsis. We propose an innovative approach for developing the diagnostics for sepsis screening and diagnosis which can be utilized by diagnostic developers in the country. Methods: Three-round Delphi method, including two online surveys and one virtual consultation, was adopted to define criteria for minimum and optimum attributes of TPPs and build consensus on characteristics. Expert panel (n=23) included infectious disease physicians, public health specialists, clinical microbiologists, virologists, researchers/scientists and technology experts/innovators. Results: We present a three-component product profile for sepsis diagnosis, (i) screening with high sensitivity, (ii) detection of aetiological agent, and (iii) profiling of antimicrobial susceptibility/resistance, in adults and neonates with an option of testing different considerations. An agreement of >75 per cent was achieved for all TPP characteristics by Delphi. These TPPs are tailored to the Indian healthcare settings and can also be extrapolated to other resource-constraint and high-disease burden settings.

Antimicrobial Resistance: The 'Other' Pandemic!

Antimicrobial resistance is projected to kill 10 million people by 2050. The biggest driver of antimicrobial resistance is excessive/unrestricted use of antimicrobials in humans and animals. Antimicrobial resistance is a problem in all types of pathogens including bacteria, mycobacteria, viruses, fungi, and parasites both globally and India and in both adults and children. The areas of greatest concern for India is the epidemic of MDR and XDR tuberculosis and resistance in gram-negative pathogens. The alarming rate of extended spectrum beta lactamase (ESBL) production in Enterobacteriales in both community and health care–associated infections is driving carbapenem use. Rates of carbapenem resistance are now signifcantly high in health care–associated gram negative pathogens with associated high mortality rates. The key solution to this antimicrobial resistance crisis needs participation of all stakeholders and lies in promoting rational antimicrobial therapy

The Emergence of Omicron: Challenging Times Are Here Again!

COVID-19 has been reported to have caused more than 286 million cases and 5.4 million deaths till date. COVID variants have appeared at regular intervals—alpha, beta, gamma, delta and now omicron. ‘Omicron’ is driving the current surge of cases in most countries including India and is poised to replace ‘delta’ the world over. This variant with more than 50 mutations is phylogenetically very diferent from other variants. The omicron variant spreads rapidly with an average doubling time of two days. The disease so far has been mild as compared with delta. Though previous infection and vaccination ofer little or no protection against infection with omicron, they do seem to partially protect against hospitalization and severe disease. Booster vaccinations have not made any notable impact on the spread of omicron and have further worsened global vaccine equity. The indirect consequences of omicron from lockdowns, restrictions, travel bans, economic losses, health care worker infections and overwhelming of health care facilities are likely to be enormous. The direct efects of omicron on children are expected to be mild like with the previous variants. However, the indirect efects on child mental, physical, and social health may be considerable owing to school closures, missed vaccinations, neglect of other diseases, etc. It is, therefore, imperative that governments take rational decisions to navigate the world through this latest crisis.

Neuroschistosomiasis: An Unusual Intracranial Space Occupying Lesion

Background: Neuroschistosomiasis is an uncommonly reported disease. Casecharacteristics: An adolescent Indian boy residing in Kenya presented with headache,visual symptoms and seizures, with MRI showing space-occupying lesions in the occipitallobe and cerebellum. Observation: Brain biopsy was diagnostic of neuro-schistosomiasis;complete recovery was seen with praziquantel and corticosteroid therapy. Message: Thiscase highlights the importance of considering epidemiology in differential diagnosis andestablishing definitive diagnosis even if it is by invasive methods

Etiology of Fever of Unknown Origin in Children from Mumbai, India

This descriptive study evaluated 49 children with fever lasting formore than 7 days at a tertiary hospital in urban Mumbai. Etiologicdiagnosis could be established in 88% of the cases. Infectionswere the causein 34 (79%)patients, 6 (14%) were diagnosed ascollagen vascular diseases, and 3 (7%) had other cause

Trypanosomiasis in a Young Infant from Rural Gujarat, India

Background: Human trypansomiasis due to infection by animal trypanosomes is rarelyreported from India. Case characteristics: We describe clinical presentation of a 2-month-old boyfrom a rat infested house in rural Gujarat who was diagnosed to be havinginfectionwith the rodent parasite Trypanosoma lewisi. Observation: The fever and parasitemiaresolved on treatment with liposomal amphotericin B, Ceftriaxone and Amikacin, and therewas no recurrence of parasitemia over a 2 month follow-up. Message: The case highlightsthe need for increased awareness and heightened surveillance for this rare zoonoticinfection

Hereditary sensory autonomic neuropathy Type IV.

Hereditary sensory autonomic neuropathy Type IV is an autosomal recessive disorder due to lack of maturation of small myelinated and unmyelinated fibers of peripheral nerves, which convey sensation of pain and temperature, therefore, resulting in self mutilation. There is anhidrosis due to lack of innervation of normal sweat glands resulting in recurrent episodes of hyperpyrexia. The clinical presentation of two children with this rare disease is described.

Management of severe malaria.

Prompt diagnosis and early institution of therapy is an important determinant of outcome in severe falciparum malaria. Thick smears are the gold standard for diagnosis; in situations where reliable microscopy is not available, tests based on HRP-2 antigen/parasite LDH are useful. As there is widespread resistance to chloroquine in P falciparum in India, the choice for specific antimalarial therapy is between quinine and artermisinin derivatives. Randomized controlled trials have not revealed any significant benefit of the artemisinin derivatives over quinine in quinine sensitive areas. Also, if quinine is administered in the recommended way, the side effects are no greater than artemisinins. However, as the artemisinin derivatives are easier to administer, their use in severe malaria in India is increasing. It is vital that we use these drugs in a rational and judicious manner to prevent development of drug resistance. Supportive care, early diagnosis and management of complications are as essential as antimalarial therapy. The role of exchange blood transfusion in the management of severe malaria is still controversial. It may be considered in the presence of high parasites counts (>10%) with multiorgan dysfunction if adequate quantities of safe blood are available.

Anemia in the newborn.

In neonatal period anemia is a complex problem owing to the unique blood picture. The erythrocytic system undergoes serial adaptation to meet progressively changing demands of oxygen in the embryo, the fetus and neonate. This leads to rapid change in normal hematological change in post-birth period. Definition of anemia is difficult because as described earlier, several important factors influence normal blood in the newborn infants. The etiology of neonatal anemia can be classified into i) hemorrhage (ii) hemolysis (iii) failure of red cell production. Severe fetal hemorrhage may accompany various placental anomalies like placenta praevia, abruptio placenta and accidental incision of placenta during the caesarian section. It is reported that 10% of all infants born following placenta praevia and 4% of infants born following abruptio placenta present with severe anemia. The passage of fetal erythrocytes in maternal circulation occurs commonly during pregnancy. In 50% of pregnancies some fetal cells are passed in maternal circulation sometimes during gestation or during birth process. Treatment of a neonate with anemia due to blood depends on the degree of hypovolemia or anemia and whether the blood loss has been acute or chronic. Newborn with pale skin should be differentiated from an asphyxiated baby.