Analysis of adenovirus DNA detected in rodent species from the Democratic Republic of the Congo indicates potentially novel adenovirus types.

Different species of adenoviruses (AdVs) infect humans and animals and are known for their role as pathogens, especially in humans, with animals, primarily rodents, often serving as model systems. However, although we know over 100 types of human AdVs, we know comparatively little about the diversity of animal AdVs. Due to the fact that rodents are the most diverse family of mammals and a standard model system for human disease, we set out to sample African rodents native to the Democratic Republic of the Congo and test them for AdV DNA using a semi-nested consensus PCR. A total of 775 animals were tested, and viral DNA was detected in four of them. The AdV DNA found belongs to three different AdVs, all being closely related to murine adenovirus 2 (MAdV-2). Considering the genetic differences of the amplicon were 9%, 11% and 19% from MAdV-2 and at least 10% from each other, they seem to belong to up to three different novel types within the Murine mastadenovirus B species. This evidence of genetic diversity highlights the opportunities to isolate and study additional AdVs that infect rodents as models for AdV biology and pathology.

High prevalence of hepatitis C virus infection and predominance of genotype 4 in rural Gabon.

Hepatitis C (HCV) molecular epidemiology is documented poorly in central African countries. In response to this, a population-based study of 319 consenting adults resident in a remote village of Gabon was undertaken (mean age: 38 years; age range: 13-85+; sex ratio: 0.74). Screening for anti-HCV antibodies was performed using ELISA and recombinant immunoblot assay. Seropositive samples were assessed further with viral load and genotyping techniques. Sixty-six (20.7%) individuals were HCV seropositive. Viral loads ranged from 600 to 24.9 million IU/ml (median: 372,500). Seroprevalence and viral loads increased significantly with age (P < 10(-5) and P < 0.003, respectively). HCV sequences of the 5'UTR genome region were obtained from 60 (90.9%) samples and NS5B region sequences were obtained from 22 (36.6%) samples. All strains belonged to subtypes of genotype 4: 4e (72.7%), 4c (13.6%), 4p (4.5%), 4r (4.5%) and one unclassified genotype 4 strain. Evolutionary analysis of the subtype 4e sequences indicates a period of raised transmission during the early twentieth century.

Identification of hepatitis B virus genome in faecal sample from wild living chimpanzee (Pan troglodytes troglodytes) in Gabon.

Non-invasive faecal sampling in the equatorial forest in Gabon allowed the first identification of the hepatitis B virus (HBV-Ch(RC170)) genome in samples collected from wild chimpanzees (Pan troglodytes troglodytes). The HBV-Ch(RCl70)sequence clustered with 100% bootstrap support with previous viral sequences obtained from Pan troglodytes subspecies. This is the first evidence of HBV infection in wild apes and confirms that the HBV-like strains thus far characterized in captive apes are directly related to those circulating in the wild.

Two distinct STLV-1 subtypes infecting Mandrillus sphinx follow the geographic distribution of their hosts.

The mandrill (Mandrillus sphinx) has been shown to be infected with an STLV-1 closely related to HTLV-1. Two distinct STLV-1 subtypes (D and F) infect wild mandrills with high overall prevalence (27.0%) but are different with respect to their phylogenetic relationship and parallel to the mandrills' geographic range. The clustering of these new STLV-1mnd sequences with HTLV-1 subtype D and F suggests first, past simian-to-human transmissions in Central Africa and second, that species barriers are easier to cross over than geographic barriers.

Synthetic peptide strategy for the detection of and discrimination among highly divergent primate lentiviruses.

We developed a simple, rapid, inexpensive, and highly sensitive and specific strategy for the detection and lineage differentiation of primate lentiviruses (PIV-ELISA). It is based on the use of two indirect ELISA methods using synthetic peptides mapping the gp41/36 region (detection component) and the V3 region (differentiation component) of four lentivirus lineages, namely SIVcpz/HIV-1 (groups M, O, N, and SIVcpz-gab), SIVmnd, SIVagm, and SIVsm/SIVmac/HIV-2. This strategy was evaluated with panels of sera originating from both humans and nonhuman primates. The human reference panel consisted of 144 HIV Western blot (WB)-positive sera in which the corresponding virus had been genotyped (HIV-1: 72 group M, 28 group O, and 6 group N; HIV-2: 21 subtype A and 10 subtype B; and 7 HIV-1+2) and 105 HIV WB-negative samples. The nonhuman primate reference panel consisted of 24 sera from monkeys infected by viruses belonging to the four lineages included in the PIV-ELISA strategy (5 chimpanzees, 5 macaques, 8 mandrills, and 6 vervets) and 42 samples from seronegative animals. Additional field evaluation panels consisted of 815 human sera from Gabon, Cameroon, and France and 537 samples from 25 nonhuman primate species. All the samples from the two reference panels were correctly detected and discriminated by PIV-ELISA. In the human field evaluation panel, the gp41/36 component correctly identified all the test samples, with 98% specificity. The V3 component discriminated 206 HIV-1 group M, 98 group O, 12 group M+O, and 128 HIV-2 sera. In the primate field evaluation panel, both gp41/36 and V3 detected and discriminated all the WB-positive samples originating from monkeys infected with SIVcpz, SIVagm-ver, SIVmnd-1, SIVmnd-2, SIVdrl, or SIVsun. These results were confirmed by genotyping in every case. Four SIV-infected red-capped mangabeys (confirmed by PCR) were correctly identified by gp41/36, but only two reacted with the V3 peptides in the absence of a specific SIVrcm V3 peptide. Addition of a V3 SIVrcm peptide discriminated all the SIVrcm-positive samples. Fourteen Papio papio samples were positive for SIVsm gp 36 and by WB, but negative by PCR, whereas three Papio cynocephalus samples were positive by gp41/36 but indeterminate by WB and negative by PCR. This combined ELISA system is thus highly sensitive and specific for antibodies directed against HIV and SIV. In addition, the V3-based serotyping results always agreed with genotyping results. This method should prove useful for studies of lentivirus prevalence and diversity in human and nonhuman primates, and may also have the potential to detect previously undescribed SIVs.

[Intrathecal synthesis of anti-Toxoplasma gondii antibodies during cerebral toxoplasmosis associated with African AIDS]. / Synthèse intrathécale d'anticorps anti-Toxoplasma gondii au cours de la toxoplasmose cérébrale associée au sida africain.

Thirty-four HIV-1-infected in-patients of the Hôpital Central des Forces Armées Congolaises, Brazzaville, Congo, hospitalized for suspected cerebral toxoplasmosis, have been evaluated for integrity of the blood-brain barrier, intrathecal synthesis of total IgG, toxoplasmic serology in blood and cerebrospinal fluid, and for intrathecal synthesis of IgG to Toxoplasma gondii. An empiric scale to gauge the possibility of clinical cerebral toxoplasmosis was used to classify the patients (+, +2, +3). Only an intrathecal synthesis of IgG to Toxoplasma gondii was found to be associated with suspected cerebral toxoplamosis: it was found in about 80% of patients, and more frequently in patients with a higher probability of disease. In contrast, alteration of the blood-brain barrier, intrathecal synthesis of total IgG and toxoplasmic serology in blood as well as in cerebrospinal fluid were not associated with suspected cerebral toxoplamosis. Taken together, these findings confirm that intrathecal synthesis of antitoxoplasmic antibodies of IgG isotype occurs in cerebral toxoplasmosis. Demonstration of intrathecal synthesis of antitoxoplasmic IgG antibodies could be used to confirm clinical diagnosis of cerebral toxoplamosis, especially in an African context, where sophisticated laboratory facilities are often lacking.

[Absence of epidemiologic interrelations between retroviral infection by HIV and human African trypanosomiasis (HAT)]. / Absence d'inter-relations épidémiologiques entre l'infection rétrovirale à VIH et la trypanosomiase humaine africaine (THA). Analyse de trois enquêtes cas-témoins réalisées en 1989 et 1990 en Afrique centrale.

Authors are reporting results from 3 control-case surveys carried out in sleeping sickness foci in Cameroon, Central African Republic and Congo. HIV seroprevalence rates are comparable among sleeping sickness patients and trypanonegative control persons. These results lead towards the absence of inter-relationships between sleeping sickness and retroviral infection.

[Retrospective study of infection by the human immunodeficiency virus in pregnant women. Future of the child and the mother]. / Etude rétrospective de l'infection par le virus de l'immunodéficience humaine chez la femme enceinte. Devenir de l'enfant et de la mère.

5.4% (108 of 2,000) women have been confirmed for HIV 1 infection in Brazzaville in 1987. 1,172 deliveries have been registered by study, 7.76% have been occurred in HIV+ women. The prevalence of miscarriages was significantly, higher in HIV+ women than in HIV- ones (p less than 0.001). The birth-weight of new-borns was not significantly different among the children born to HIV+ and HIV- mothers. There were the various probable reasons of death of children born to HIV+ mothers. More frequently the respiratory affections with persistent hyperthermia were noticed. During the follow-up, in all groups of age, the fever with failure of thrive were the most frequent signs (50%) with pneumopathy. The clinical picture was completed by diarrhoea after six months of live.

[Clinical and developmental aspects of acquired immunodeficiency syndrome in the Congo (the experience of the medical service of the Hôpital Central des Armées Pierre Mobengo - Brazzaville)]. / Aspects cliniques et évolutifs du syndrome d'immunodépression acquise au Congo (expérience du service de médecine de l'Hôpital Central des Armées Pierre Mobengo - Brazzaville).

During a period of 20 months, 204 cases of AIDS were diagnosed among adults in the Medicine Department of the Pierre Mobengo Armed Forces Central Hospital, Brazzaville. The authors review the clinical and evolutive aspects in admitted patients during these period of time, taking into consideration the problems of diagnosis, treatment and monitoring, according to the conditions of practice. Individuality of AIDS in Central Africa is underlined by its different features. AIDS strikes heterosexual people with multiple partners, with a sex-ratio near to 1. In a patient more often cachectic and febrile, some digestive manifestations occurred, mainly diarrheal, early, neurological, of bad prognosis. Pulmonary manifestations (above all tuberculosis superinfection) and cutaneous manifestations often characteristic, are less frequent and mainly different from the ones observed in Europe and North America. Fast evolution is underlined. These characteristics of AIDS in Central Africa, of course subordinate to the medical context, seem mainly linked to a peculiarity of the disease, in close relationship with the density of the infection, diathesis and opportunistic environment, all very different.

[Hematologic parameters during human immunodeficiency virus (HIV) infection in various Congolese subpopulations]. / Etude de paramètres hématologiques au cours de l'infection par le virus de l'immunodéficience humaine (VIH) dans différentes sous-populations Congolaises.

Study of 220 haematological profiles in women, men and children was realized in National Laboratory of Public Health and in Central Army Hospital in Brazzaville. The red cells count the haemoglobin level, the leucocytes and eosinophilia leukocyte counts in each sub-group of HIV+ and HIV- patients were compared. The anemia is important in HIV+ patients (Center for Diseases Control IV). The hyperleukocytosis and lymphocytosis of child and lymphopenia of adult are confirmed. The interest of surveillance of haematological parameters is as important for HIV+ asymptomatic individuals (Center for Diseases Control II) as for those of Center for Diseases Control IV group. The study of haematological profile is the interesting factor of diagnostic and prognosis.

[Bilharziasis and human immunodeficiency virus infection in Congo]. / Bilharziose et infection par le virus de l'immunodeficience humaine au Congo.

To assess the relationship between schistosomiasis and human immunodeficiency virus (HIV) infection, a cross-sectional study of HIV seroprevalence was carried out in 1992 in a village in the Bouenza region of the Congo where there is a high incidence of urinary schistosomiasis. No correlation was found between eggs in urine and positive serology for HIV in the 895 adults examined nor between positive schistosome serology and positive HIV serology. The incidence of frank schistosome infection (eggs in urine and positive blood tests) was significantly lower in patients with positive HIV serology (3.5%) than in patients with negative HIV serology (6.7%). Similarly the mean number of eggs in urine was significantly lower in patients with positive HIV serology (3.6 eggs per ml) than in patients with negative HIV serology (26.6 eggs per ml) (p < 0.01). These observations suggest that HIV infection limits schistosome development and decreases antibody production. Further study will be needed to confirm these findings.

[Impact of AIDS on the resurgence of tuberculosis and reduced availability of hospital beds in Brazzaville (Congo)]. / Impact du SIDA sur la recrudescence de la tuberculose et la réduction de la disponibilité des lits hospitaliers à Brazzaville (Congo)

Our objective was twofold: firstly to evaluate the impact of AIDS on the annual increase of tuberculosis morbidity in Brazzaville; and secondly, to show its consequences on the reduced availability of hospital beds for patients treated for diseases nonrelated to AIDS. This retrospective study included 541 tuberculosis patients who were treated from 1988 to 1992 in the Department of Medicine at the Military Central Hospital in Brazzaville. The serum of all patients was tested by ELISA and Western blots for the presence of HIV. HIV and tuberculosis coinfection were very frequent (more than 30% of all AIDS cases), particularly among young people (20-45 years old). Extrapulmonary tuberculosis cases (37%) have become almost as frequent as pulmonary tuberculosis forms (42.8%) among HIV positive patients, and the clinical picture is often atypical. Tuberculosis morbidity is increasing annually because of AIDS. The longer the tuberculosis patients with AIDS remain in the hospital, the fewer beds are available for other patients. For the public health programs against AIDS in developing countries, this is becoming an urgent problem to resolve.

[Toxoplasmosis and cytomegalovirus serology in patients infected with HIV in Congo]. / Sérologie de la toxoplasmose et du cytomégalovirus des malades infectés par le VIH au Congo.

Cerebral toxoplasmosis and cytomegalovirus (CMV) infection are very frequent in AIDS. Biological markers of toxoplasmosis and CMV were studied in blood and cerebrospinal fluid (CSF) of 121 HIV-positive and 35 HIV-negative patients in the Central Hospital of the Congolese Army in Brazzaville. In the case of clinically suspected cerebral toxoplasmosis, the simultaneous presence of specific IgG antibodies in the blood and in the CSF can be considered as having complementary diagnostic value (PPV = 63.3%, NPV = 89.9%). The symptomatology of AIDS is very polymorphous and includes various etiological factors; as a result it is very difficult to estimate the responsibility of cytomegalovirus in the absence of positive viral culture, even with the simultaneous presence of specific IgG antibodies in the blood and CSF (PPV = 75.7%, NPV = 54.6%).

Hepatitis viruses in non-human primates.

BACKGROUND: Previous epidemiological studies of rural human populations in Gabon reveal a high prevalence of human hepatitis A, B, C and D viruses. In order to investigate the prevalence of the blood-born hepatitis viruses in apes and monkeys living in the same area, we performed an epidemiological survey of HBV, HCV and HDV in wild-born non-human primates. METHODS: We tested 441 wild-born non-human primates from Gabon and Congo and 132 imported monkeys for the presence of serological markers of HBV, HCV and HDV infections. RESULTS: None of Cercopithecidae monkeys were reactive against HBV/HDV and HCV. In contrast, 29.2% of wild-born great apes (154 chimpanzees and 14 gorillas) were positive for HBV serological markers. Nine chimpanzees were in the replicative phase of HBV infection. None of these HBV infected chimpanzees exhibited symptoms or significant changes in serum clinical chemistry related to HBV infection. CONCLUSIONS: The negativity to HCV-related viruses and the negativity of the Cercopithecidae species tested against HBV/HDV do not allow us to definitively rule out the presence of an animal counterpart of human hepatitis viruses in non-human primates.

Prevalence and clinical presentations of arthritis in HIV-positive patients seen at a rheumatology department in Congo-Brazzaville.

OBJECTIVE: To determine the prevalence and clinical presentations of rheumatic manifestations in HIV-infected patients seen at a rheumatology department in Congo-Brazzaville. METHODS: Over a one-year period, all patients admitted to the Brazzaville Teaching Hospital's rheumatology unit underwent serologic testing for the HIV by ELISA confirmed by Western blot. Standard criteria were used to classify the inflammatory joint diseases seen during the study period. RESULTS: A total of 171 patients, 85 men and 86 women, were tested. The age range was 16 to 81 years, with a mean of 42.1 years. HIV tests were positive in 39 patients, 24 men and 15 women, with a mean age of 31.2 years, accounting for 22.8% of the overall patient population and for 35.1% of all patients with inflammatory rheumatic syndromes. HIV infection stage as determined based on Centers for Disease Control criteria was i.v. in 35 patients and II in the remaining four patients. Of the 39 HIV-positive patients, 32 had HIV-related arthritis, two had reactive arthritis, two had staphylococcal septic arthritis and three had infectious discitis. Of the 72 HIV-negative patients with inflammatory rheumatic syndromes, 22 had septic arthritis, 18 had infectious discitis, five had reactive arthritis, four had rheumatoid arthritis, four had gout, two had poststreptococcal rheumatic disease, one had juvenile chronic arthritis and 16 had unclassifiable arthritis. None of the remaining 60 HIV-negative patients had inflammatory joint manifestations. CONCLUSION: HIV infection was both the leading reason for admission and the leading cause of arthritis. Acute, febrile, asymmetric, nondeforming, nonerosive polyarthritis of the small and large joints responsive to nonsteroidal antiinflammatory drug therapy was the most common clinical pattern of arthritis in HIV-positive patients. Reactive arthritis, septic arthritis and infectious discitis were rarely seen and had no specific features as compared to HIV-negative patients. Patients with arthritis should be tested for HIV infection. It follows that rheumatologists need to know how to provide counselling about HIV testing and how to disclose the results to their patients. They also need to be familiar with the management of HIV infection and to direct careful attention to the prevention of HIV transmission in health care facilities.

SIVrcm infection of macaques.

In a prior report, we described the isolation and characterization of SIVrcm, a distinct primate lentivirus found in a household pet Red-Capped Mangabey (RCM) in Gabon. SIVrcm is divergent from HIV-1 and HIV-2/SIV families of primate lentiviruses. In this report, additional in vitro replication studies and the results of SIVrcm infection in macaques are presented. SIVrcm causes little cytopathic effedct in Molt 4 Clone 8 cells and in rhesus and human PBMCs. In vivo, SIVrcm is non-pathogenic after 200 days in rhesus macaques and after one year in cynomolgous macaques, but does cause a chronic infection in both macaques.

Occurrence of hepatitis viruses in wild-born non-human primates: a 3 year (1998-2001) epidemiological survey in Gabon.

Hepatitis B and C infections are endemic in human population in central Africa, particularly in Gabon. The aim of this study was to determine the prevalence of hepatitis B virus (HBV) and eventual occurrence of hepatitis C virus (HBC)-related strains in a variety of wild-born non-human primates living in Gabon and Congo. Plasma samples were screened for HBV and HCV markers. A non-invasive method of DNA extraction from faeces followed by specific HBV-DNA amplification was developed to study this infection in wild troops of chimpanzees and gorillas. No HCV infection in non-human primates, wild-born or captive, was detected among 596 samples tested. No HBV infection could be detected in samples tested and obtained from Cercopithecidae. In contrast, 14.7 and 42.2% of wild-born chimpanzees in Gabon and Congo were infected with HBV or had evidence of past HBV infection. At Centre International de Recherches Médicales (CIRMF) Primate Centre, 32.1% of chimpanzees and gorillas were HBV positive or had evidence of past infection. In the cases with past infection, 5.9% wild-born and 8.3% at CIRMF harboured HBV-DNA despite the presence of neutralizing HbsAb. Together with previous findings, we confirm the high HBV prevalence not only in humans but also in chimpanzees and gorillas in Gabon and Congo.

Natural infection of a household pet red-capped mangabey (Cercocebus torquatus torquatus) with a new simian immunodeficiency virus.

A seroprevalence survey was conducted for simian immunodeficiency virus (SIV) antibody in household pet monkeys in Gabon. Twenty-nine monkeys representing seven species were analyzed. By using human immunodeficiency virus type 2 (HIV-2)/SIVsm, SIVmnd, and SIVagm antigens, one red-capped mangabey (RCM) (Cercocebus torquatus torquatus) was identified as harboring SIV-cross-reactive antibodies. A virus isolate, termed SIVrcm, was subsequently established from this seropositive RCM by cocultivation of its peripheral blood mononuclear cells (PBMC) with PBMC from seronegative humans or RCMs. SIVrcm was also isolated by cocultivation of CD8-depleted RCM PBMC with Molt 4 clone 8 cells but not with CEMx174 cells. The lack of growth in CEMx174 cells distinguished this new SIV from all previously reported sooty mangabey-derived viruses (SIVsm), which grow well in this cell line. SIVrcm was also successfully transmitted (cell free) to human and rhesus PBMC as well as to Molt 4 clone 8 cells. To determine the evolutionary origins of this newly identified virus, subgenomic pol (475 bp) and gag (954 bp) gene fragments were amplified from infected cell culture DNA and sequenced. The position of SIVrcm relative to those of members of the other primate lentivirus lineages was then examined in evolutionary trees constructed from deduced protein sequences. This analysis revealed significantly discordant phylogenetic positions of SIVrcm in the two genomic regions. In trees derived from partial gag sequences, SIVrcm clustered independently from all other HIV and SIV strains, consistent with a new primate lentivirus lineage. However, in trees derived from pol sequences, SIVrcm grouped with the HIV-1/SIVcpz lineage. These findings suggest that the SIVrcm genome is mosaic and possibly is the result of a recombination event involving divergent lentiviruses in the distant past. Further analysis of this and other SIVrcm isolates may shed new light on the origin of HIV-1.