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Biomedical subjects

M Kombila

Publications and source records attributed to M Kombila.

At least 19 recordsLinked to original sources

Association of a new mannose-binding lectin variant with severe malaria in Gabonese children.

Mannose-binding lectin (MBL2) variants that decrease the plasma level of the protein or encode dysfunctional proteins are frequently associated with the severity of a number of infections and autoimmune disorders. The high frequencies of these variants in most populations of the world are probably maintained by some selective advantage against widespread diseases. We found 14 new MBL2 allelic haplotypes, two of them with non-synonymous variants, by screening 136 children with uncomplicated malaria, 131 children with severe malaria and 39 older healthy schoolchildren. We also found a significant association of a novel variant with susceptibility to severe malaria (P=0.010). Increased MBL plasma levels and corresponding MBL2 genotypes were associated with lower concentration of several cytokines and chemokines in plasma of malaria patients. We suggest that malaria could have been one of the evolutionary driving forces shaping the MBL2 polymorphism in the African population.

Alleles↗

Lactic acidosis in Gabonese children with severe malaria is unrelated to dehydration.

BACKGROUND: Hyperlactatemia is an important and common complication of severe malaria. We investigated changes in fluid compartment volumes in patients with severe malaria and control patients with the use of bioimpedence analysis. METHODS: We estimated extracellular water and total body water volumes in a total of 180 children: 56 with severe malaria, 94 with moderate malaria, 24 with respiratory tract infection, and 6 with severe diarrhea. RESULTS: There was a mean (+/-SD) decrease in total body water volume of 17+/-24 mL/kg (or 3% of total body water volume) in patients with severe malaria. This compares with a mean (+/-SD) decrease in total body water volume of 33+/-28 mL/kg (or 6% of total body water volume) in patients with severe diarrhea. There was no increase in extracellular water volume in patients with severe malaria, suggesting no significant intravascular volume depletion in patients with severe malaria. There was no relationship between lactatemia and any changes in fluid compartment volumes. CONCLUSIONS: The changes in fluid volumes that were observed are unlikely to be of physiological significance in the pathophysiology of severe malaria.

Acidosis, Lactic↗

[Opportunistic diseases in HIV-infected patients at the Jeanne Ebori Foundation in Libreville, Gabon].

The purpose of this study was to determine the frequencies of opportunistic diseases among AIDS patients at the Jeanne Ebori Foundation (JEF) in Libreville, Gabon. A total 6313 file of patients treated in the internal medicine unit between 1994 and 1998 were analyzed. Findings showed that the main diseases related to AIDS classified according to seroprevalence were as follows: purigo (100%), cerebral toxoplasmosis (100%), oral candidiaisis (88%), bacteremia (87.8%), shingles (84.6%), minor salmonelosis (72%), and tuberclosis. The main diagnoses unrelated to AIDS at the JEF according to seroprevalene were typhoid (9.4%), common pneumonia (28%), bacterial meningitis (26.3%, hepatitis B (20.0%), and malaria (14%). In addition to these diseases there were nine cases of Kaposi's sarcoma, four cases of isosporosis, two cases of cryptococcosis, two cases of herpes Varicella, one case of cryptosporidiosis, and one case of isosporosis. The incidence of opportunistic disease was high in our study and must be taken in drug procurement.

AIDS-Related Opportunistic Infections↗

[Onchocerciasis in the area of Lastourville, Gabon. Clinical and entomological aspects].

The African Programme for Onchocerciasis Control (APOC) has implemented a series of surveys aimed at evaluating the long-term impact of its activities. The region of Lastourville (Gabon) is one of the selected sites for this study. A total of 886 persons was examined for skin lesions, and 459 out of them participated in detailed ocular examinations. Blackflies were collected during one year and dissected. Although the focus was found to be hypoendemic (prevalence of nodules: 7.7%), the frequency of onchodermatitis was relatively high. The lesions of the anterior segment of the eye were rare, but the prevalence of optic nerve disease, and of choroido-retinal lesions reached 5.2 and 2.7%, respectively. The annual transmission potential (2,171 infective larvae per man) was high, when compared with the results recorded in the human population. This may be due to the presence of Onchocerca spp. of animal origin in the blackflies. These results indicate that in the area of Lastourville, though regarded as the main focus of onchocerciasis in Gabon, the disease is relatively mild.

Adolescent↗

Metabolic complications of severe malaria.

Metabolic complications of malaria are increasingly recognized as contributing to severe and fatal malaria. Disorders of carbohydrate metabolism, including hypoglycaemia and lactic acidosis, are amongst the most important markers of disease severity both in adults and children infected with Plasmodium falciparum. Amino acid and lipid metabolism are also altered by malaria. In adults, hypoglycaemia is associated with increased glucose turnover and quinine-induced hyperinsulinaemia, which causes increased peripheral uptake of glucose. Hypoglycaemia in children results from a combination of decreased production and/or increased peripheral uptake of glucose, due to increased anaerobic glycolysis. Patients with severe malaria should be monitored frequently for hypoglycaemia and treated rapidly with intravenous glucose if hypoglycaemia is detected. The most common aetiology of hyperlactataemia in severe malaria is probably increased anaerobic glucose metabolism, caused by generalized microvascular sequestration of parasitized erythrocytes that reduces blood flow to tissues. Several potential treatments for hyperlactataemia have been investigated, but their effect on mortality from severe malaria has not been determined.

Acidosis, Lactic↗

[Pulmonary bilharziosis due to Schistosoma haematobium: pitfalls of species diagnosis. A case report from Libreville, Gabon].

The purpose of this report is to describe a case of pulmonary schistosomiasis treated at la Fondation Jeanne Ebori in Libreville, Gabon. This case is exceptional due to the rarity of the disease and the schistosomiasis agent involved. The patient was a 47-year-old woman who presented with recurrent right-sided pneumonia 6 months after initial hospitalization and nonspecific antimicrobial therapy. Her general status was altered by hyperthermia, right chest pain, and repetitive bouts of hemoptysia. Because etiological diagnosis could not be achieved and clinical condition was deteriorating, the decision was taken to perform exploratory thoracotomy. Based on operative findings, medial and lower lobectomy was performed. Histological examination demonstrated granulomatous inflammatory lesions due to bilharziosis. Infection was attributed to Schistosoma haematobium that is the most common agent in pulmonary localizations. However Ziehl coloration raised the possibility of involvement of Schistosoma intercalatum that has never been observed in the lung and of a hybrid species. Natural hybridization between S. haematobium and S. intercalatum and the presence of active transmission of the Schistosoma hybrid has been suspected in Gabon.

Animals↗

In vitro activity of amphotericin B, fluconazole and voriconazole against 162 Cryptococcus neoformans isolates from Africa and Cambodia.

In order to determine the potential role that various antifungal agents might have in the management of cryptococcosis in tropical areas, the in vitro susceptibility of Cryptococcus neoformans isolates from Africa ( n=52) and Cambodia ( n=110) to three antifungal agents (amphotericin B, fluconazole and voriconazole) were compared using the E-test method. The results of this study (i) confirm the value of the E-test for testing the in vitro susceptibility of C. neoformans towards voriconazole; (ii) provide the first evidence demonstrating good activity of amphotericin B, fluconazole and voriconazole against Cambodian isolates; and (iii) show there are differences in susceptibility between African and Asian C. neoformans isolates, with Cambodian isolates appearing less susceptible to the agents tested but with amphotericin B maintaining good activity.

Africa↗

Identification and specificity of a 38 kDa Loa loa antigenic fraction in sera from high-microfilaraemic Gabonese patients.

Circulating antigens isolated from sera of three high-microfilaraemic ( Loa loa) Gabonese patients were fractionated by gel filtration. A major component (38 kDa) was identified after SDS-PAGE and immunoblotting using sera of amicrofilaraemic patients with high level of antimicrofilariae Loa loa antibodies. The 38 kDa fraction was not found in the sera of parasitised patients or healthy controls. We looked for the 38 kDa antigen in the various stages of the filarial life cycle and found it in extracts of Loa loa microfilariae but not in somatic extracts of Loa loa male and female adult worms. This fraction could be used as a diagnostic marker in loiasis for amicrofilaraemic patients.

Animals↗

No evidence of Wolbachia endosymbiosis with Loa loa and Mansonella perstans.

Endosymbiotic Wolbachia bacteria from different filarial species, including major pathogens of humans such as Wuchereria bancrofti, Brugia malayi and Onchocerca volvulus, seem to play an important role in the development, viability and fertility of these worms. Wolbachia trigger inflammatory host responses as well as adverse reactions against standard treatment regimens and are therefore under investigation as novel treatment targets. We investigated whether Wolbachia are also endosymbiotic in Loa loa and Mansonella perstans. In both male and female adult L. loa, we found no evidence of bacteria by light or transmission electron microscopy. Furthermore, Wolbachia-specific PCR was negative in both L. loa and M. perstans microfilariae. The absence of Wolbachia in both filarial species therefore discourages the use of antibiotics as an adjunct or alternative approach to current treatment concepts for both loiasis and mansonelliasis perstans.

Animals↗

Plasma glutamine and glutamate concentrations in Gabonese children with Plasmodium falciparum infection.

BACKGROUND: Low plasma glutamine levels in critical illness, neonates and burns patients are associated with poor outcome and increased risk of intercurrent infection. AIM: To investigate the relationship between plasma glutamine/glutamate levels and severity/outcome of malaria. DESIGN: Two-hospital prospective study, with both febrile and healthy controls. METHODS: We measured plasma glutamine and glutamate concentrations in 239 Gabonese patients: 145 children with malaria (86 with severe, 36 with moderate and 23 with uncomplicated disease), 42 healthy children, 44 febrile controls and eight healthy adults, and related findings to conventional markers of disease severity such as plasma lactate. RESULTS: Median (IQR) plasma glutamine was lower in uncomplicated falciparum malaria and in moderate malaria than in healthy controls: 353 (287-474) and 379 (293-448) vs. 485 (428-531) micromol/l, respectively; p<0.01 for both malaria groups vs. controls. In contrast, plasma glutamine was within the normal range in those with severe malaria and in febrile control children: 431 (342-525) and 472 (338-547) micromol/l, respectively. Furthermore, plasma glutamine was significantly higher in the children who died with malaria than in survivors: 514 (374-813) (n=12) vs. 399 (316-475) micromol/l (n=133), respectively; p=0.001. There were no significant differences in plasma glutamate concentrations between any of the study groups. DISCUSSION: In severe malaria, there was a positive correlation between plasma glutamine and lactate levels (p=0.009, r=0.281). This correlation may reflect impaired gluconeogenesis. Glutamine supplementation is probably not justified in severe P. falciparum infection.

Biomarkers↗

[Analysis of snake bite envenomations in Gabon].

In tropical zones, snakebites are considered serious. Exotic snakes are characterised by the poisonousness of their venom and its abundance. Death is rapid in some cases and in others the sequelae are serious. Worldwide, there are more than 5 million victims per year, with 50,000 deaths registered and 400,000 amputations. The frequency and severity of snakebites in Gabon remain unknown. It is estimated that there is an average of one snakebite every 4 days, thus some 91 snakebites per year. Through a study carried out at the Libreville Hospital, we evaluated the frequency, severity, and fatality of this circumstantial pathology. A retrospective study conducted on 157 patients admitted for snakebite at the Intensive Care Unit of the Libreville Hospital was carried out between 1998 and 2001. 1.32% of all admissions were for snakebites. Signs of venom poisoning were observed in 27 patients (17%), versus 130 cases without envenomation. The majority of cases were in adults (78%) and children affected (22%) were aged mainly 6-14 years. The snakebite season usually coincided with the rainy season. During this period, 19 cases were registered. Snakebites occurred during the daytime (93%), in the fields in 20 cases (75%) or in the home courtyard (25%). The victims lived in town in 25 cases (93%). Antivenom was used in all envenomation cases, and the result was favourable in 23 cases (18%) but unfavourable in 4 (15%).

Adolescent↗

Ferrocene-chloroquine analogues as antimalarial agents: in vitro activity of ferrochloroquine against 103 Gabonese isolates of Plasmodium falciparum.

The in vitro activities of ferrochloroquine, chloroquine, quinine, mefloquine, halofantrine, amodiaquine, primaquine, atovaquone and artesunate were evaluated against Plasmodium falciparum isolates from children with uncomplicated malaria from Libreville (Gabon), using an isotopic, micro, drug susceptibility test. The IC(50) values for ferrochloroquine were in the range 0.43-30.9 nM and the geometric mean IC(50) for the 103 isolates was 10.8 nM (95% CI 8.6-13.5 nM), while the geometric means for chloroquine, quinine, mefloquine, amodiaquine and primaquine were 370 nM, 341 nM, 8.3 nM, 18.1 nM and 7.6 microM, respectively. Ferrochloroquine was active against P. falciparum isolates, 95% of which showed in vitro resistance to chloroquine. Weak positive significant correlations were observed between the responses to ferrochloroquine and that to chloroquine, amodiaquine and quinine, but too low to suggest cross-resistance. There was no significant correlation between the response to ferrochloroquine and those to mefloquine, halofantrine, primaquine, atovaquone or artesunate. Ferrochloroquine may be an important alternative drug for the treatment of chloroquine-resistant malaria.

Animals↗

Comparison of methods for the rapid laboratory assessment of children with malaria.

Rapid diagnosis and accurate quantification of Plasmodium falciparum parasitemia are important for the management of malaria. The assessment of disease severity also depends on evaluation of metabolic indexes such as blood glucose and lactate concentrations. Here we describe an accurate and rapid alternative to conventional thick film examination (Lambaréné method). We also assess near-patient methods for measuring blood glucose (OneTouch) and lactate (Accusport). The accuracy of the Lambaréné method is similar to that of thin films. Results from the OneTouch glucose meter also are in good agreement with a YSI 2300 reference meter. Overall, the Accusport lactate meter agrees poorly with the YSI 2300 reference meter. However, the sensitivity and specificity to detect hyperlactatemia (blood lactate > or = 5 mmol/L) are 0.94 and 0.98, respectively.

Blood Glucose↗

[Causes of adult acute bacterial diarrhea in an internal medicine department in Libreville, Gabon].

This retrospective study of patients treated between 1992 and 1996 was undertaken as a preliminary step to identifying the main bacterial causes of diarrheal disease in Libreville, Gabon. A total 371 files showing positive stool cultures were analyzed. From an epidemiological standpoint, data showed that the high risk population was young people of both sexes. The incidence of diarrhea was correlated with climatic conditions with an endemic-epidemic pattern characterized by peak activity during the rainy season. In the vast majority of cases, the underlying etiology was gastroenteritis due to invasive organisms. The most commonly identified agents were salmonellae (46.6%) and Shigellae (44.2%). Treatment should focus on rehydration. Fluoro-quinolones were the most commonly indicated drugs for antimicrobial treatment but cotrimoxazole was often useful. In general, the prognosis of bacterial diarrhea is favorable provided that it is treated early and concurrent conditions are taken into account.

Acute Disease↗

[Evaluation of efficacy and tolerance of amodiaquine versus chloroquine in the treatment of uncomplicated malaria outbreak in children of Gabon].

We conducted a prospective study from September 1997 to January 1998 in Libreville (Gabon). Fifty-three (53) children with uncomplicated P. falciparum malaria were included and divided into two groups. The first group (27 patients) was treated with amodiaquine and the second (26 patients) with chloroquine. The efficacy and tolerance of amodiaquine 30 mg/kg base over 3 days (10 mg/kg daily) and chloroquine 25 mg/kg base over 3 days (10 mg/kg day 0, 10 mg/kg day 1, 5 mg/kg day 3) were estimated at days 7 and 14. Clinical examination and parasitaemia were assessed on days 0, 1, 2, 3, 7, 14. Haematological and biochemical parameters were determined on days 0 and 7. Amodiaquine was shown to be more effective than chloroquine in clinical response and ridding patients of parasites: adequate clinical response was significantly higher with amodiaquine than chloroquine [100% (27/27) versus 45% (9/20), p < 0.0005]. Rates for early treatment failure (ETF) and late treatment failure (LTF) were respectively 35% and 12% with chloroquine. The parasitological success rate was significantly higher with amodiaquine than chloroquine on days 7 [93% (25/27) versus 62% (13/21), p < 0.008] and 14 [100% (13/13) versus 44% (4/9), p < 0.01]. The RI resistance type was 7% in the amodiaquine group. The rate of in vivo chloroquino-resistance was 53%, essentially of RII and RIII type. Overall, the two drugs were well tolerated.

Adolescent↗

In vitro susceptibility of African isolates of Plasmodium falciparum from Gabon to pyronaridine.

The in vitro activity of pyronaridine was evaluated against 62 isolates of Plasmodium falciparum from Libreville, Gabon using an isotopic, drug susceptibility microtest and was compared with amodiaquine, chloroquine, quinine, and halofantrine activities. The mean 50% inhibitory concentration (IC50) values of the 62 isolates from Gabon to pyronaridine was 3.0 nM (95% confidence interval [CI] = 2.1-3.9). Pyronaridine was less potent against chloroquine-resistant isolates than chloroquine-susceptible isolates but more potent than chloroquine against chloroquine-resistant parasites. The cut-off value for in vitro reduced susceptibility to pyronaridine was an IC50 > 15 nM. Two isolates (3%) showed an IC50 > 15 nM. A significant positive correlation was found between the activities of pyronaridine and chloroquine (r2 = 0.26, P < 0.001), pyronaridine and quinine (r2 = 0.36, P < 0.001), pyronaridine and amodiaquine (r2 = 0.55, P < 0.001), and pyronaridine and halofantrine (r2 = 0.50, P < 0.001). This correlation suggests in vitro cross-resistance or at least in vitro cross-susceptibility, which is not necessarily predictive of cross-resistance in vivo. The present in vitro findings require comparison with those of clinical studies.

Adolescent↗