With the outbreak of the Second World War hostilities, Köberle was attached as field pathologist to the XII Army Group of the Wehrmacht in 1940 and served in the fronts of France, Belgium, Poland and Russia.
He was able to acquire during this period an enormous experience on the pathology of infectious diseases (bacterial dysentery, typhus, typhoid fever, tularemia and malaria) as well as war-inflicted wounds, and performing more than four thousand autopsies.
Even though 40 years had passed since its discovery, little was known about the peculiar manifestations of the chronic phase of the disease, such as megaesophagus, megacolon, cardiomegaly, heart ventricular aneurysm, achalasia, etc., and the mechanism of the causation of these several pathologies.
By making good use of the extensive caseload of fatalities due to Chagas disease in the region of Ribeirão Preto and Southern Minas Gerais, where it was endemic and widely prevalent at the time, Köberle studied initially the dilation pathologies of the digestive tract and proved, by extensively quantifying the number of neurons of the autonomic nervous system in the Auerbach's plexus, that: 1) they were strongly reduced all over the digestive tract; 2) that megacolon and megaesophagus appeared only when there was a reduction of over 80% and 55% of the number of neurons, respectively; 3) these pathologies appeared as a result of the disruption of the neurally integrated control of peristalsis (muscular annular contraction) in those parts where a strong force is necessary to impel the luminal bolus of food or feces; and 4) European idiopathic megaesophagus and Chagas megaesophagus appeared to have the same etiology, namely the degeneration of the Auerbach's myoenteric plexus.
Studying the typical features of the Chagasic myocardium pathology, characterized by damage to its electrical conduction pathways, heart arrhythmia, aneurysm of the ventricular apex, cardiomegalia and sudden death by ventricular fibrillation, Köberle and his group of collaborators were able to prove that they were caused also by an extensive denervation of the parasympathetic (55%) and sympathetic (35%) intrinsic cardiac nervous networks, leading to a control imbalance of contraction, cardiac failure, cardiomegalia and hypoxia.