Journal of Pharmacogenomics & Pharmacoproteomics

In 1990, in the Democratic Republic of the Congo, Mobutu’s regime was at its end and political, social, cultural country environment was very bad. The country was under general international embargo for political reasons. All partners of education of Congolese universities left the country and all of our laboratories lacked of equipment. Medical situation was also bad because of the HIV general infection which was at its top in the country.

It’s in that period of time that we started at the Laboratory of Toxicology of the University of Kinshasa a cross-sectional study of a strange disease present in DR Congo since a few decades, characterized by huge digestive and extra-digestive pathologies, considered by Congolese population as a result of massive criminal poisonings throughout the country. Internal heat, suffocation, mental confusion, heart pain, intense tiredness and loose of weight were the principal symptoms of that phenomenon.

During the 3^rd Euro case reports in Valencia Spain, in 2016, the strange medical case taking place in DR Congo has been presented. Indeed, contrary to the conviction of the Congolese population about the existence of massive criminal poisonings, throughout the country, we incredibly observed and demonstrated, in 2010, a surprising and unexpected Helicobacter pylori epidemic with numerous extra-digestive pathologies.

This paper deals with the presentation made during the 5^th Clinical and Medical Euro case reports held in Paris, France in 2017 September 07 to 08, explaining picturesque meanders by which our research work passed, before getting appropriate results. According to the presentation, it will focus first on a brief summary of Helicobacter pylori phenomenon described in Valencia and hypothesis raised for the better knowledge of Helicobacter pylori infection, at the international level. Afterwards the influence and consequences of some delaying factors will be presented. Finally, two extra-digestive Helicobacter pylori cases observed in our study will be discussed.

Study design and sample

This paper is based on a cross-sectional study conducted on Karoo patients received at the Laboratory of Toxicology of the University of Kinshasa from January 2005 to June 2016. The study protocol has been submitted to the Internal Review Board of the Faculty of Pharmaceutical Sciences of the University of Kinshasa and it has been conducted according to the principles of the Helsinki Declaration (Ethical Principles of Medical Research Involving Human Subjects) as amended in 2013.

Variables of study

Questionnaire for data collection included three parts. The first part concerned socio-demographic variables: age, sex, educational level and marital status. The second part described “Karoo phenomenon”: symptoms, origin, circumstances of poisoning, traditional diagnostic and treatment, opinions of Karoo patients on this phenomenon. The third part addressed the relationship between “Karoo phenomenon” and Helicobacter pylori. Scientific parameters were: saliva pH, toxicological screening (Thin layer chromatography, and UV spectrophotometer), Blood sedimentation rate, Alanine Aminotransferase test (ALAT), Aspartate Aminotransferase test (ASAT), Urea, Creatinine, Helicobacter pylori (Chromatographic serological method), Hemoglobin, and Glucose.

Case reports

Two cases were reported: a patient’s case, and a post-mortem case. The two cases have been selected for their especial feature. Patient’s case concerned a woman of 36 year’s old, single, employed in a private communication enterprise. The post-mortem case concerned a 40 years old man, married, self-employed. They were both positive to Helicobacter pylori with extra-digestive evident signs, displayed in photos in attachment.

Population of study

Table 1 shows that the population of study included 402 patients received at the Laboratory of Toxicology of the University of Kinshasa from January 2005 to June 2016, 277 males and 125 females. Patients from 20 to 50 years old were more represented in the population of study but there were also 21 patients beyond 50 years old and 4 children less than 5 years old. Unmarried patients were 181 (45%) while the currently married patients were 193 (48%). The number of patients received was in ascendant progression: 40 (9.9%) from 2005 to 2009, 56 (13.6%) from 2010 to 2013 and 306 (76.1%) from 2013 to 2016.

Table 1: Socio-demographic variables (n=402).

Characteristics of Karoo poisoning

Symptoms: Symptoms were diversified. They were digestive but most extra-digestive as well, divided in general and nervous symptoms (Table 2).

Table 2: Symptoms collected in DR Congo.

Opinions of patients on Karoo phenomenon

Table 3 presents opinions of patients on Karoo phenomenon. Most patients thought that Karoo symptoms could last months (275, 68.4%) or years (58, 14.4%). The eastern of the country was identified unanimously as the principal site of Karoo poisoning (402, 100%). Four principal symptoms were identified: internal heat (282, 70.1%), bitterness of food and beverages (257, 69.9%), intense tiredness (275, 68.4%) and inexplicable loss of weight (269, 66.9%). In case of Karoo poisoning, preference was to visit traditional practitioners instead of going to the hospital. Three traditional diagnostic tests were pointed out, all conducted on patients’ saliva. Traditional treatment was centered on the honey, sometimes mixed to lemon and garlic juice (402, 100%). The recourse to the Laboratory of Toxicology was directed by two main reasons: traditional treatment failure (388, 96.5%) and the need of scientific diagnosis (346, 86%).

Table 3: Opinions of patients on Karoo phenomenon (n=402).

Biological parameters

Table 4 shows biological parameters checked. Toxicological screening and Saliva alkalinity determination were performed in all the patients from 2005 to 2016. The others biomarkers (H. pylori, sedimentation rate, hemoglobin, ASAT, ALAT, creatinine and urea) were recorded only since 2013, in 306 patients. H. pylori and saliva alkalinity were positive to all patients examined. Sedimentation rate was high (H. pylori was obtained in 280 patients (91.5%). Symptoms were also cleared in 280 patients (91.5%). Resistance rate to treatment was then 8.5%. Iron deficiency anemia was present in 80 patients (26.1%).

Table 4: Results of biological parameter.

Case reports parameters

Patient’s case parameters

Table 5: Patients’ case parameters.

Post-mortem case parameters

Table 6: Post-mortem case parameters.

Summary of main findings

The strange phenomenon characterized by huge extra-digestive pathologies, current in Democratic Republic of Congo, considered as massive criminal poisoning, appeared actually caused by Helicobacter pylori. (ii) Its characteristics and symptoms have been collected (Table 2). (iii) Helicobacter pylori outbreak in DRC needed environment activator factors. (v) Patients’ saliva was alkalized by gas ammonia flying up from stomach to mouth. (vi) Gas ammonia and carbon dioxide are responsible of huge patients’ extra-digestive pathologies. Carbone dioxide combines causticity and redoubtable fatal asphyxia power, as demonstrated in the post-mortem case.

Helicobacter pylori infection

Helicobacter pylori, is well known worldwide. It largely colonizes humans since immemorial time, in both developing and developed countries [1-24]. It’s widely involved in gastritis, asymptomatic for most infected individuals. A small proportion of infected individuals develop more dangerous gastritis involving peptic ulceration and gastric malignancy [22,25-33]. Helicobacter pylori is responsible for tremendous morbidity and mortality throughout the world [6,7,12,14-16]. Normally originated in Africa, Helicobacter pylori has been carried with human populations around the world after their departure from Africa [26,29]. Helicobacter pylori infected persons increase risk of developing gastric cancer. Many factors and cofactors influence gastric cancer development [8,10,32-34]. Helicobacter pylori virulence is under the control of Helicobacter pylori gene factors [25,27,30,31]. There is actually an important change in the relationships between helicobacter pylori and humans, caused by modern life change in gut micro-ecology [19,29]. In Africa, Helicobacter pylori infection displays a specificity called “African enigma” related to the fact that, in spite of a high Helicobacter pylori contamination in Africa, often from early childhood, gastric cancer prevalence is inexplicably low [6,17,21].

DRC Helicobacter pylori phenomenon

Congolese population is, until now, convinced that the phenomenon current in DR Congo is a consequence of massive criminal poisonings. Yet, our study established, in 2010, an unexpected interesting link with Helicobacter pylori. According to Table 4, the 362 patients received at the Laboratory of Toxicology of the University of Kinshasa for poisoning suspicion, were all positive to Helicobacter pylori. They were all characterized by huge extra-digestive pathologies (Table 2). Main pathologies identified were: internal heat (282, 70.1%), bitterness of food and beverages (257, 69.9%), intense tiredness (275, 68.4%) and inexplicable loss of weight (269, 66.9%). Following other hypothesis was raised in our study: (i) numerous extra-digestive pathologies observed, indicated a free and massive passage of ammonia and carbon dioxide to the blood. (ii) Ammonia and carbon dioxide released in stomach by the reaction urea-urease, in gaseous state, should be eliminated in stools. (iii) In case of constipation however, ammonia and carbon dioxide, still in gaseous state, could go up along the esophagus to the mouth and lungs and from there to the blood stream. (iv) A double intoxication then occurs, justifying numerous extra-digestive pathologies described in Table 2. (v) This statement is in perfect harmony with recent literature which reports more and more extra-digestive pathologies linked to Helicobacter pylori [23,28,35-41].

Proposed improvements on Helicobacter pylori infection

Under the light of our study, some following improvements would be proposed for best Helicobacter pylori infection understanding: (i). Helicobacter pylori infection should be named Helicobacter pylori toxic-infection to take count of the intoxication component present in many cases of Helicobacter pylori infection as frequently stated in recent literature. (ii). Helicobacter pylori extra-digestive symptoms should be definitely recognized as part of Helicobacter pylori infection. (iii) Passage of Helicobacter pylori toxins in blood via lungs way should be acknowledged. (iv). Helicobacter pylori treatment should be reevaluated to take in count the intoxication component. Our study suggested that toxicological eliminating treatment should always be combined to Helicobacter pylori medical eradication treatment. (v). the development of a rapid Helicobacter pylori diagnosis method based on ammonia identification in saliva and in stools could be useful.

An atypical wandering research work

Our research work took a long time before getting suitable results because, mainly, of unfavorable political, social, cultural and scientific environment of the end of Mobutu’s regime in DR Congo and the war it generated. The international political embargo imposed to DR Congo since 1990, provoked lack of equipment, lack of financial means for research and lack of useful South-North collaboration. Secondly, Karoo poison was not only unknown but invisible physically as well.

Thirdly, rumors, traditional believe of Congolese population and cupidity of traditional practitioners played an important impairment role. For example, as reported in Table 3, modern medicines were reputed to be inefficient against Karoo poison. The use of modern medicines, especially by perfusion, was even thought to rapidly lead to death. The consequence was that in many villages, most in the eastern region of the country, people avoided going to the hospital, for any disease. As it could be guessed, HIV/AIDS, tuberculosis and malaria took big advantage of this situation.

Some symptoms reported in Table 2, like intense tiredness, anorexia and most significant loss of weight was commune to Karoo phenomenon and to HIV. The confusion with HIV was a major complication factor in our study.

Opinion of some Congolese medical staff, denying findings concerning the role of Helicobacter pylori in Congolese Karoo phenomenon was also an important source of wandering.

As displayed in Figures 1-6, patient’s case main pathology was feet swelling. Helicobacter pylori was positive, blood sedimentation rate high (85 mm/h), alanine aminotransferase, aspartate aminotransferase, urea and creatinine, were in normal range (Table 5). No hypertension and diabetes diseases. Swelling was accompanied by internal heat in stomach and thorax, dizziness, headache, reflex cough, and intense tiredness (Table 5). Feet swelling was attributed to Helicobacter pylori CO₂ toxin, after its passage to the blood via the lungs way, as stated in this study. Activated charcoal guaranteed feet deflating within ten days (Table 5).

Figure 1: Gut distending photo forensic medicine institute/Kinshasa.

Figure 2: Stomach distending photo forensic medicine institute/Kinshasa.

Figure 3: Brain Congestion photo forensic medicine institute/Kinshasa.

Figure 4: Right Lung Congestion photo forensic medicine institute/Kinshasa.

Figure 5: Fingers and toes cyanosis photo forensic medicine institute/Kinshasa.

Figure 6: Feet swelling photo Shafali/Kinshasa.

The post-mortem case was received, from Forensic Medicine Institute of General Hospital of Kinshasa for toxicological analysis, after a suspect death. Death occurred suddenly, at home, during the night, after the return from a friend’s party. Immediately after death, stomach inflated extremely at an incredible speed. Autopsy findings were unexpected and amazing. Autopsy statement revealed full of abnormalities, notably: Gut distending, Stomach distending, Brain congestion, Lungs congestion, Cyanosis of lips, fingers and toes, Tongue biting, Pallor of Hands palms and pallor of sole of the feet, Cardiomegaly, Eyes red coloration, Nose bleeding, Gastric bleeding (Table 6). All those abnormalities were identified as sign of double intoxication by gas ammonia and carbon dioxide. Death occurred bluntly after brutal carbon dioxide asphyxia. Helicobacter pylori was incriminated, as the deceased was a known Helicobacter pylori chronic gastritis patient. Those two cases, selected among many others, were significant testimony of the findings of this study.

Our research work was very time consuming because it did face many obstacles. In spite of all problems faced, we did never give up. Results got after a so long period of time beyond 20 years of wandering, seem impressive. It’s necessary not to forget that in spite of all disturbances in Sub-Saharan African countries, many scientific researchers are there, trying painfully to contribute to the improvement of scientific world knowledge.

We think necessary to develop more scientific collaboration and networks between researchers from developing and developed countries, far beyond political considerations.

We encourage young research workers, to never give up. They have to know that in any research work, without a bit wandering mind, phenomenal results could never be achieved.