Inborn errors of immunity, previously described as primary immune deficiencies, represent a group of diseases with inadequate development of immune responses to infectious diseases. This is due to a genetic disease that affects immune cell development and function. Characteristics of these diseases include failure to thrive, in addition to recurrent, persistent, and multipathogen infectious diseases. The CHAMPS series is a multicountry 20-year project implemented in sites with under-5 mortality rates of more than 100 per 1,000 live births. In this series, we seek to estimate the burden of inborn errors of immunity, in the Child Health and Mortality Prevention, Surveillance (CHAMPS) series.
This has been running for 7 years. In this project, all natural under-5 mortalities are recruited, and postmortem testing, consisting of minimally invasive tissue sampling (MITS) and detailed, advanced pathological testing, is performed within a defined health and demographic surveillance site (HDSS). In Kenya, these activities are performed within Siaya (Karemo) and Kisumu (Manyatta) HDSS, representing rural and urban deaths. In addition, risk factors are sought from clinical and demographic data. MITS specimens obtained are brain, lung, liver, blood, and cerebrospinal fluid. From these deaths, we identified potential inborn errors of immunity based on postneonatal age (child and infant) and clinical characteristics (history of previous child deaths, recurrent infections, and persistent disease) and presence of malnutrition. The final diagnosis, assigned as the immediate cause of death, and underlying causes of death are considered.
In Kenya, a total of 1,602 subjects, out of an eligible population of 1,727, were recruited, and MITS performed. Of these, infant deaths were 352, consisting of 217 males and 172 females, while child deaths were 362, consisting of 192 males and 170 females. In this population, malnutrition, malaria, HIV disease, congenital birth defects, diarrheal diseases, and lower respiratory tract infections are major underlying causes of death. Malnutrition, malaria, HIV disease, and birth defects are major immediate causes of disease. In these cases, suboptimal clinical case management is a major contributor to mortality. Multipathogen infectious disease is common where a diagnosis of malnutrition and HIV disease are presented. In this series, two cases appear to fulfill diagnostic criteria for inborn errors of immunity. The first case is a 4-month-old male infant who is severely malnourished, with disseminated CMV disease and disseminated candida infection. The child presented with history of fever, with a temperature of 39 degrees. This child had undergone early weaning; the mother was a teenage pregnancy and had used herbal medicines. The second case is a 5-month-old female child whose cause of death is multipathogen sepsis and fungemia, with disseminated intravascular coagulation identified as a direct complication of these infections. There was also bowel gangrene and abdominal wall birth defects (gastroschisis). In this series, there are no incidences of infantile mycobacterial infections associated with universal BCG vaccination.
Due to high malaria, malnutrition, and HIV disease, and the limited nature of the MITS technique, potential cases of errors of immunity are difficult to identify. Two cases identified had multiple infections, consisting of disseminated fungal and bacterial infections, while one has additional disseminated CMV disease. As quality of care improves as a consequence of data- to action-driven interventions, more cases may be identified in this population.
