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Biomedical subjects

E Karita

Publications and source records attributed to E Karita.

At least 19 recordsLinked to original sources

Evaluation of the resazurin microtiter assay for rapid detection of ofloxacin resistance in M. tuberculosis.

OBJECTIVE: To evaluate the performance of the colorimetric resazurin microtiter assay (REMA) method for the detection of ofloxacin resistance. METHODS: A panel of 120 multidrug-resistant Mycobacterium tuberculosis strains was tested blindly by the REMA method and compared with the results obtained using the BACTEC 460 method. RESULT: A very good correlation was observed between the two methods. CONCLUSION: The REMA method is simple, rapid and can be an inexpensive alternative procedure for the rapid detection of anti-tuberculosis drug resistance in laboratories with limited resources.

Anti-Bacterial Agents↗

Characterization of CD8+ T lymphocytes in chronic HIV-1 subtype A infection in Rwandan women.

We examined CD8+ T lymphocyte characteristics in Rwandan women who have survived HIV-1 subtype A infection for 8-13 years without antiretroviral therapy. HIV-1 subtype A gag-specific IFN-gamma expressing CD8+ T lymphocytes were detectable in PBMC from 5 of 7 women and there was a strong positive association (r = 0.9262; p < 0.001) between these cells and plasma viral load. CD8+ T cells of these HIV-positive women produced more RANTES and MIP-1beta than cells from HIV-negative donors. However, extremely low levels of perforin (0.88 +/- 0.93%) were produced by CD8+ T lymphocytes from the infected women compared with HIV-negative controls (42.86 +/- 11.0%; p < 0.001). The percentages of CD8+ CD45RA+ perforin+ and CD8+ CD45RA+ CD27-lymphocytes were also much lower in the HIV-infected women compared with HIV-negative controls. Therefore, the inability of CD8+ T cells to control HIV may, in part, be dependent on insufficient generation of effectors from HIV-specific CD8+ T cells. Also, the lack of perforin in CD8+ T cells is linked with persistent CD27 expression, suggesting impaired maturation and impairment in cytolytic activity in chronic HIV-1 infection.

CD4-Positive T-Lymphocytes↗

Predictors of HIV seropositivity following intrapartum voluntary counseling and testing among Rwandan women.

We investigated risk factors associated with HIV infection in women who accepted voluntary counselling and testing (VCT) intrapartum. A survey questionnaire containing information on sociodemographic characteristics was administered to parturients at the Central Hospital Kigali after informed consent had been obtained. Participants were then offered VCT for HIV, and those who accepted were informed of their results. Of the 427 eligible participants, 317 accepted VCT (74.2%). The results of 312 (98.4%) of these women were obtained and 50 tested positive for HIV, yielding an HIV seroprevalence of 16.0% intrapartum. Women who had been pregnant three or more times were three times as likely to test positive for HIV in comparison to those of lower parity (OR=2.9; 95% confidence interval (CI)=1.1 - 8.0). This finding contradicts earlier studies performed antenatally among women of childbearing age and pregnant women in general. This may be attributable to some inadequacy in the existing health-care infrastructure to effectively detect HIV in multiparous women antenatally, or may represent a signal that a change in the nature of the epidemic in Rwanda is occurring.

Adult↗

Novel alleles at the lymphotoxin alpha (LTalpha) locus mark extended HLA haplotypes in native Africans.

Genetic variations at the closely related tumor necrosis factor alpha (TNFalpha or TNF) and lymphotoxin alpha (LTalpha, formerly TNFbeta) loci have been well documented in various human populations, and several haplotypes spanning the MHC class I and class II loci are known to carry specific TNF alleles. Genotyping of the TNFc microsatellite within the first intron of LTalpha in 285 Rwandans and 319 Zambians revealed two predominant alleles, c1 at frequencies of 0.598 and 0.683 and c2 at 0.384 and 0.307, respectively. Overall, the distribution of TNFc genotypes containing the major alleles conformed well to the Hardy-Weinberg equilibrium in both cohorts. Two previously unrecognized minor TNFc alleles were also detected: the first, designated c0, was found in 10 native Africans and was the only allele present in 10 chimpanzees; the second, designated c3, was seen in 6 other African patients. Further genotyping at loci for HLA class I, class II, and for transporters associated with antigen processing, subunit 1 (TAP1) in those 16 individuals suggested a tight, stable extended haplotype involving c0 and 26Asn (LTalpha)-TNF3 (TNF promoter -238A and -308G)-DRB1*1503-DQB1*0602-TAP1.2 (333Val)-TAP1.4 (637Gly). The c3 allele was observed on another extended haplotype with 26Thr (LTalpha)-TNF1 (TNF promoter -238G and -308G)-DQB1*0102-DQB1*0501-TAP1*0101 (333Ile and 637Asp). The c3-tagged haplotype further extended to Cw*15 at the HLA class I C locus, but no specific A or B alleles could be unambiguously assigned. Positive associations between c2 homozygosity and HIV-1 seronegative status in both Rwandans and Zambians (odds ratio = 2.03 and 2.00, p = 0.04 and 0.07, respectively) had little effect on the haplotype assignments. These findings suggest a preferential expansion of the human TNFc dinucleotide (CT/AG) repeat sequence and further imply the existence of two extended MHC lineages that have not been disrupted by recombinations.

Africa↗

TAPI polymorphisms in several human ethnic groups: characteristics, evolution, and genotyping strategies.

Genetic variations in the locus encoding the transporter associated with antigen processing, subunit 1 (TAP1), were systematically studied using samples from Caucasians, Africans, Brazilians, and compared with data from chimpanzees. PCR-amplified genomic sequences corresponding to the 11 exons were analyzed by single-strand conformation polymorphism (SSCP) and sequencing. Six nonsynonymous and 2 synonymous single nucleotide polymorphisms (SNPs) were found to be common in one ethnic group or another, and they involved codons 254 (Gly-GGC/Gly-GGT) in exon 3, 333 (Ile-ATC/Val-GTC) in exon 4, 370 (Ala-GCT/Val-GTT) in exon 5, 458 (Val-GTG/Leu-TTG) in exon 6, 518 (Val-GTC/Ile-ATC) in exon 7, 637 (Asp-GAC/Gly-GGC), 648 (Arg-CGA/Gln-CAA) and 661 (Pro-CCG/Pro-CCA) in exon 10. At each SNP site the sequence listed first was predominant in all ethnic groups. Several SNPs segregated on the same chromosome regardless of populations and species. Together, the SNPs produced 5 major human TAP1 alleles, 4 of which matched the officially recognized alleles *0101, *02011, *0301, and *0401; the 5th allele differed from each of those by at least 4 SNPs. Overall, TAP1*0101 was the predominant allele in all ethnic groups, with frequencies ranging from 0.667 in Zambians to 0.808 in US Caucasians. The TAP1*0401 frequency showed the greatest difference between Africans (0.221-0.254) and Caucasians (0.033), with Brazilians (0.058) fitting in the middle. Consistent with earlier work based on Caucasians and gorillas, *0101 appeared to be the newest human TAP1 allele, suggesting a dramatic spread of *0101 into all human populations examined. Characterization of TAP1 polymorphisms allowed the design of a PCR-based genotyping scheme that targeted 7 SNP sites and required 2 separate genotyping techniques.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Genotyping TAP2 variants in North American Caucasians, Brazilians, and Africans.

The protein forms of transporter associated with antigen processing, subunit 2 (TAP2), differ either by amino acid substitutions (Thr374Ala, Ile379Val, Ile467Val, Thr565Ala, Val577Met, Cys651Arg, and Ala665Thr) or by a truncation (Gln687Stop) of 17 amino acid residues at the C-terminus. Nonsynonymous single nucleotide polymorphisms (N-SNPs) causing these amino acid variations except 577Val were detected in genomic DNA samples from North American Caucasians (n = 76), Brazilians (n = 148), Rwandans (n = 285), and Zambians (n = 117). Exclusive (100%) and nearly exclusive (>95%) linkage disequilibrium was seen with a number of N-SNPs. The average heterozygosity at any given dimorphic site ranged from 7.3% to 44.6%, and at least four N-SNPs showed clear population specificity. N-SNP combinations alone led to the identification of 16 relatively common alleles, which appeared to form at least three lineages. Further analyses of 101 cDNA samples from Brazilians detected nine expressed TAP2 alleles, four of which matched the official assignments. Genetic complexity at the TAP2 locus was further enhanced by two out of five synonymous SNPs (S-SNPs), especially the GGT386GGG (Gly) that had similar heterozygosity rates in Caucasians (28.9%), Rwandans (33.3%), and Zambians (33.3%). Overall, distribution of both synonymous and nonsynonymous SNPs in the various ethnic groups examined here conformed well to the Hardy-Weinberg equilibrium, and between 57.9% and 77.0% of subjects in each ethnic group were heterozygous with two TAP2 alleles predicted to differ by at least one amino acid residue. Such complexity of TAP2 polymorphisms, in the form of SNPs as well as alleles, is likely to complicate the analyses of disease associations and haplotype structures in the HLA class II region.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Antimicrobial susceptibilities of Neisseria gonorrhoeae in Kigali, Rwanda, and trends of resistance between 1986 and 2000.

BACKGROUND: Plasmid-mediated and chromosomal-mediated resistance of Neisseria gonorrhoeae to penicillin, tetracycline, thiamphenicol, and trimethoprim-sulfamethoxazole has spread dramatically in Africa. Monitoring of antimicrobial susceptibility is a key element in the control of sexually transmitted diseases. GOAL: To document antimicrobial susceptibilities of gonococci isolated during the past 15 years in Kigali, Rwanda. STUDY DESIGN: Minimal inhibitory concentrations of recently collected gonococcal isolates of eight antimicrobials were determined. The results were compared with data collected for isolates obtained since 1986. RESULTS: In 1986, 35% of the gonococcal isolates were penicillinase-producing N gonorrhoeae. Tetracycline-resistant N gonorrhoeae appeared in 1989. The prevalence of penicillinase-producing N gonorrhoeae and tetracycline-resistant N gonorrhoeae increased significantly to 70.5% and 89.2%, respectively. Chromosomal resistance to penicillin, tetracycline, and thiamphenicol increased temporarily, then decreased significantly. Chromosomal resistance to trimethoprim-sulfamethoxazole appeared in 1988 and increased to 21.6%. All the isolates were susceptible to ceftriaxone, ciprofloxacin, spectinomycin, and kanamycin. CONCLUSIONS: This study illustrated the rapidly increasing frequencies of penicillinase-producing N gonorrhoeae and tetracycline-resistant N gonorrhoeae. Chromosomal resistance to thiamphenicol and trimethoprim-sulfamethoxazole excludes these drugs as alternative treatment. Programs for antimicrobial susceptibility surveillance of N gonorrhoeae should urgently be established in Africa.

Drug Resistance, Microbial↗

Sexual practices of HIV discordant and concordant couples in Rwanda: effects of a testing and counselling programme for men.

As part of a longitudinal investigation, the husbands and cohabiting male partners of 684 Rwandan women were recruited to participate in an HIV testing and counselling programme. All of the women and 256 of the men (37%) had previously received standard testing and generic counselling services. In this project, all of the men participated in an extensive, male-focused counselling programme. This included 428 men who were receiving testing and counselling for the first time. Interview responses indicated that rates of condom use during sexual intercourse increased dramatically at the one-year follow-up assessment for the serodiscordant couples. This effect was especially strong for couples whose male partners were receiving testing and counselling for the first time. Rates of condom use also increased substantially in seroconcordant HIV-positive couples whose partners had both been tested previously. Women in couples with at least one seropositive partner reported lower rates of coercive sex by their male partners after they completed the counselling programme. Male-focused and couple-focused testing and counselling programmes appear to be effective in reducing risky sexual behaviours in heterosexual couples, even if one or both partners have received testing and counselling services previously.

Adult↗

Ocular manifestations of infection with the human immunodeficiency virus in an African pediatric population.

PURPOSE: To describe the ocular manifestations of HIV/AIDS infection in an African pediatric population. METHODS: From 1984 to 1990, all children with HIV infection attending the Department of Pediatrics of the 'Centre Hospitalier de Kigali', Rwanda, were referred to the Department of Ophthalmology for ophthalmic examination. RESULTS: A total of 162 HIV-infected children were examined. The overall rate of ophthalmic involvement was 54%. The most common finding was a perivasculitis of the peripheral retinal vessels, observed in 38% of the patients. Cytomegalovirus (CMV) infection of the retina was diagnosed in three patients. Isolated cotton-wool spots of the retina were not observed. Ophthalmic herpes zoster and conjunctival xerosis responding to vitamin A administration were each seen in two patients. One third of a subset of children tested for lacrimal function had evidence of decreased tear secretion. CONCLUSION: Our data, in agreement with other series reported in the literature, indicate that cotton-wool spots and CMV retinitis, the most common ocular manifestations of HIV/AIDS in adults, are much less prevalent in children. The high incidence of perivasculitis in the present series, not observed or only seen in a few cases in other series, suggests that this ocular sign is more prevalent in African children. Our working hypothesis is that perivasculitis of the retinal vessels, lymphoid interstitial pneumonitis, parotitis, and lacrimal gland involvement are the expression of a diffuse infiltrative lymphocytosis syndrome, similar to what has been described in adults.

AIDS-Related Opportunistic Infections↗

Characteristics of HLA class I and class II polymorphisms in Rwandan women.

OBJECTIVE: To define HLA class I and class II polymorphisms in Rwandans. METHODS: PCR-based HLA genotyping techniques were used to resolve variants of HLA-A, B, and C to their 2- or 4-digit allelic specificities, and those of DRB1 and DQB1 to their 4- or 5-digit alleles. RESULTS: Frequencies of 14 A, 8 C, and 14 B specificities and of 13 DRB1 and 8 DQB1 alleles were >/=0.02 in a group of 280 Rwandan women. These major HLA factors produced 6 haplotypes extending across the class I and class II regions: A*01-Cw*04-B* 4501-DRB1*1503-DQB1*0602 (A1-Cw4-B12- DR15 - DQ6), A * 01 - Cw * 04 - B * 4901 -DRB1 * 1302-DQB1*0604 (A1-Cw4-B21-DR13-DQ6), A*30 - Cw*04 - B*15 - DRB1*1101 - DQB1*0301 (A19-Cw4-B15-DR11-DQ7), A*68-Cw*07-B* 4901-DRB1*1302-DQB1*0604(A28-Cw7-B21- DR13 - DQ6), A*30 - Cw*07 - B*5703 - DRB1* 1303-DQB1*0301(A19 - Cw7 - B17 - DR13 - DQ7), and A*74-Cw*07-B*4901-DRB1*1302-DQB1* 0604 (A19-Cw7-B21-DR13-DQ6), respectively. Collectively, these extended haplotypes accounted for about 19% of the total. Other apparent class I-class II haplotypes (e.g., Cw*17-B*42-DRB1*0302-DQB1*0402, Cw*06- B*58-DRB1*1102-DQB1*0301, and Cw*03- B*15-DRB1*03011-DQB1*0201) did not extend to the telomeric HLA-A locus, and other 3-locus class I haplotypes (e.g., A*68-Cw*04-B*15, A*74-Cw*04-B*15, and A*23-Cw*07-B*4901) completely or partially failed to link with any specific class II alleles. DISCUSSION: Frequent recombinations appeared to occur between the three evolutionarily conserved HLA blocks carrying the class I and class II loci. The HLA class I profile seen in Rwandans was not directly comparable with those known in the literature, although the class II profile appeared to resemble those in several African populations. These data provide additional evidence for the extensive genetic diversity in Africans.

Alleles↗

HLA class I homozygosity accelerates disease progression in human immunodeficiency virus type 1 infection.

Polymorphic products of HLA class I genes restrict cytotoxic T lymphocyte responses to the constantly evolving spectrum of HIV-1 antigens. Accordingly, homozygosity at class I loci can reduce the repertoire for such HLA-dependent interactions, leading to accelerated disease progression. To test this hypothesis we studied subjects from two distinct HIV/AIDS cohorts: 140 Dutch homosexual men and 202 Rwandan heterosexual women followed up to 13 years from HIV-1 seroconversion. We performed intermediate- and selective high-resolution molecular typing at HLA class I (A, B, and C) and high-resolution typing at HLA class II DRB1 and DQB1. Homozygosity at the HLA-A or -B locus or both was found at increasingly high frequency among individuals with successively more rapid progression to late-stage HIV-1-related conditions. In the combined cohorts (n = 342) the odds ratio (OR) due to HLA-A or -B antigen homozygosity in rapid versus slow progressors was 3.8 (p = 0.003); for Dutch men alone the OR was 3.5 (p = 0.102), and for Rwandan women the OR was 4.1 (p = 0.009). In contrast, homozygous genotypes at either HLA-C, DRB1, or DQB1 alone, or DRB1-DQB1 haplotypes, did not exert any deleterious effect on HIV-1 disease progression. These findings suggest strongly that diversity in addition to sequence specificity at HLA-A and -B loci can influence the rate of disease progression following HIV-1 infection.

Cohort Studies↗

Maternal humoral factors associated with perinatal human immunodeficiency virus type-1 transmission in a cohort from Kigali, Rwanda, 1988-1994.

OBJECTIVES: to study different parameters of humoral immunity responses in the serum of 39 human immunodeficiency virus type-1 infected pregnant women from Kigali, (Rwanda) in correlation with perinatal transmission. METHODS: this study was done between 1988 and 1994. Thirty nine HIV-1 infected women, 18 transmitting (T) and 21 non-transmitting (NT) mothers, have been chosen based on the quantity of sera available for analysis. Maternal data were collected at the time of delivery or during the preceding month. Quantification of viral load was performed by the signal amplification bDNA assay. Specific reactivity of antibody was tested against recombinant p24 protein and five different synthetic peptides from gp120 and gp41 based on HIV LAI-strain sequences. Neutralization assays were performed against laboratory (RII strain of the HIV-1 C subtype) and primary strains (two NSI and one SI of the HIV-1 A subtype). Antibody Dependent Cellular Cytotoxicity assay was performed with CEM.NK(R) cells against a laboratory HIV-1 strain. RESULTS: absence of correlation regarding maternal viral load, or viral subtype and vertical transmission was observed. By contrast, the CD4/CD8 ratio was significantly higher in non-transmitting mothers compared to transmitting mothers. Moreover, high anti-p24 antibody avidity was correlated with a lower risk of perinatal transmission. Furthermore, transmission risk appeared significantly higher with reactivity of serum samples to linear epitopes of gp41 (amino acids 566-582, 578-594), whereas risk appeared lower with reactivity to the immunodominant domain of gp41 (amino acids 597-609). No significant difference was observed in titres of antibody neutralizing primary isolates (two NSI (non syncitium inducer) and one SI (syncitium inducer) of the HIV-1 A subtype) and laboratory strain (RII strain, of the HIV-1 C subtype) between transmitting and non-transmitting mother's sera. In addition, titres of Antibody Dependent Cellular Cytotoxicity were similar in transmitting versus non-transmitting mothers. However, high Antibody Dependent Cellular Cytotoxicity titres were correlated with a good clinical status of children. CONCLUSIONS: three parameters such as high CD4/CD8 ratio, high anti-p24 antibody avidity and high reactivity against the immunodominant epitope of gp41 have been shown to be correlated with no perinatal transmission. High Antibody Dependent Cellular Cytotoxicity titres appeared to be linked to a good clinical status of children after birth. One parameter, reactivity against two linear epitopes of gp41, appeared to be correlated with vertical transmission.

Acquired Immunodeficiency Syndrome↗

Allelic variants of human beta-chemokine receptor 5 (CCR5) promoter: evolutionary relationships and predictable associations with HIV-1 disease progression.

Variability in the natural history of HIV-1 infection has been repeatedly associated with genetic variants in the beta-chemokine receptor 5 (CCR5) locus. While CCR5 coding sequences have demonstrated relatively limited variation, sequences of its promoter appear polymorphic in all major populations. Our studies revealed five major CCR5 promoter alleles with distributions that differed widely among the four distinct ethnic groups from Kigali, Rwanda and Bronx, New York. In particular, promoter allele P*0103 (G59029-T59353-T59356-A59402-C59653) was largely restricted to black subjects. The promoter allele P*0202 (A59029-C59353-C59356-A59402-T59653) was tightly linked to the slightly less frequent CCR2b-641, a variant of the CCR2b gene, which is about 12.7 kbp upstream from the promoter region. Another closely related promoter allele P*0201 (A59029-C59353-C59356-A59402-C59653) exclusively carried the far less common CCR5-delta 32, a 32-bp deletion in the CCR5 coding sequence 2 kbp downstream from the promoter. The homozygous P*0201/*0201 genotype can be predicted as a risk factor for more rapid disease progression. Among human, chimpanzee, pig-tailed macaque, and sooty mangabey promoter allelic sequences, the apparent ancestral lineage of the promoter sequence (G59029-T59353-C59356-A59402-C59653 = human P*0102) was highly conserved across the primate species analyzed here while P*0201 and P*0202 arose more recently than the other three major alleles. Further effort to establish the mechanism by which CCR chemokine receptor polymorphisms govern the initiation and pathogenesis of primate lentivirus infection apparently requires fully detailed genotypic characterization of the affected populations.

Alleles↗

Low birthweight in infants born to African HIV-infected women: relationship with maternal body weight during pregnancy: Pregnancy and HIV Study Group (EGE).

The effect of maternal HIV infection on birthweight was estimated. In the prenatal clinic of the Centre Hospitalier de Kigali, HIV screening was proposed to women with a gestational age (GA) of less than 28 weeks. HIV-infected (HIV+) and uninfected (HIV-) women were recruited, when they consented. At inclusion, socioeconomic, obstetrical data, and body weight were collected, a clinical examination was performed, and tests for sexually transmitted diseases (STDs) and malaria were performed. Two prenatal visits were made, at 28-32 and 32-36 weeks, with clinical data and weight measurement. At delivery, birthweight, body length, and head circumference of the infant were documented. At inclusion and at the second follow-up visit, HIV+ women (N = 177) weighed less than HIV- women (N = 194) (p = 0.004). Mean birthweight in infants born to HIV+ women was 2947 g (SD = 429) and 3104 g (SD = 461) in infants born to HIV- women (p = 0.001). Frequencies of low birthweight (LBW, weight < 2500 g), prematurity (GA < 37 weeks, according to Finnström score at birth), and intrauterine growth retardation (defined by LBW and GA > or = 37 weeks) were higher in infants born to HIV+ women than to HIV- women (p = 0.009, 0.01, and 0.053, respectively). In multivariate logistic regression, the association between maternal HIV infection and LBW disappeared (p = 0.61), while low GA (p = 0.01) and low last prenatal weight (p = 0.01) were independant risk factors of LBW. LBW in infants born to HIV+ women could be partly attributable to impaired maternal weight. These results underline the need for nutritional surveillance and dietary counselling, hoping to improve the prognosis of pregnancy in HIV+ women, regardless of other therapeutic interventions.

Adult↗

Cervical dysplasia and HIV type 1 infection in African pregnant women: a cross sectional study, Kigali, Rwanda. The Pregnancy and HIV Study Group (EGE).

OBJECTIVE: To study the prevalence of cervical squamous intraepithelial lesions (SILs) and their association with HIV-1 infection and immunodeficiency among pregnant women in Kigali, Rwanda. METHODS: As part of a cohort study on the impact of HIV-1 infection on pregnancy outcome, HIV-1 seropositive (HIV+) and seronegative (HIV-) pregnant women were enrolled during the last trimester of pregnancy at the maternity ward of the Centre Hospitalier de Kigali from July 1992 to August 1993. At inclusion, women were screened for sexually transmitted diseases (STDs)--syphilis, Neisseria gonorrhoeae, chlamydia trachomatis, Trichomonas vaginalis. CD4+ lymphocyte counts were measured and a Papanicolaou smear performed. RESULTS: Papanicolaou smear was interpretable in 103 HIV+ women and 107 HIV- women. Prevalence of SILs was significantly higher in HIV+ women than in HIV- women: 24.3% v 6.5% (odds ratio = 4.6; 95% CI: 1.8-12.3). SIL+ women (n = 32) tended to have more STDs than SIL- women (n = 178), but this did not reach a statistical difference: 37.5% and 24.7% respectively (p = 0.13). They also had a mean CD4 count significantly lower than SIL- women (623 and 784 CD4+ cells x 10(6)/l, respectively; p = 0.02). CONCLUSION: SILs were HIV related and the association with immunosuppression was statistically significant. Prevalence of SILs was high in this population of pregnant women with high HIV/STDs prevalence. Screening policy for STDs and SILs in African women should be assessed in prenatal care.

AIDS-Related Opportunistic Infections↗

Natural history of human immunodeficiency virus type 1 infection in children: a five-year prospective study in Rwanda. Mother-to-Child HIV-1 Transmission Study Group.

OBJECTIVE: To compare morbidity and mortality of human immunodeficiency virus type 1 (HIV-1)-infected and HIV-1-uninfected children and to identify predictors of acquired immunodeficiency syndrome (AIDS) and death among HIV-1-infected children in the context of a developing country. DESIGN: Prospective cohort study. SETTING: Maternal and child health clinic of the Centre Hospitalier de Kigali, Rwanda. PARTICIPANTS: Two hundred eighteen children born to HIV-1-seropositive mothers and 218 born to seronegative mothers of the same age and parity were enrolled at birth. OUTCOME MEASURES: Deaths, clinical AIDS, nonspecific HIV-related manifestations, and use of health care services. RESULTS: Fifty-four infected and 347 uninfected children were followed up for a median of 27 and 51 months, respectively. With the exception of chronic cough, the risk of occurrence of nonspecific HIV-related conditions was 3 to 13 times higher in infected than in uninfected children. The recurrence rate and severity of these findings were increased systematically in infected infants. Estimated cumulative risk of developing AIDS was 28% and 35% at 2 and 5 years of age, respectively. Estimated risk of death among infected children at 2 and 5 years of age was 45% and 62%, respectively, a rate 21 times higher than in uninfected children. Median survival time after estimated infection was 12.4 months. Early infection, early onset of HIV-related conditions, failure to thrive, and generalized lymphadenopathy were associated with subsequent risk of death and/or AIDS, whereas lymphoid interstitial pneumonitis was predictive of a milder disease. CONCLUSIONS: In Africa, HIV-1-infected children develop disease manifestations early in life. Specific clinical findings are predictive of HIV-1 disease, AIDS stage, and death. Bimodal expression of HIV-1 pediatric disease is encountered in Africa, as in industrialized countries, but prognosis is poorer. human immunodeficiency virus infection, children, vertical transmission, natural history, Africa.

AIDS-Related Opportunistic Infections↗

Serum retinol and HIV-1 RNA viral load in rapid and slow progressors.

Few studies have addressed the relation between serum vitamin A levels and HIV disease progression. Thirty HIV-infected women in Rwanda were studied over a time span of 26 to 99 months. Fourteen subjects seroconverted and died of HIV-related disease at a mean of 44 months (range, 26-69 months) after their first HIV-positive test and were termed "rapid progressors," (RPs). A comparison group of 16 "slow progressors" (SPs) were HIV-positive at the time of their first HIV serology and had asymptomatic HIV infections at a mean of 96 months (range, 93-99 months) after their first HIV serology. Baseline mean serum retinol values were the same in RPs and SPs: 0.65 + 0.08 micromol/L versus 0.67 + 0.09 micromol/L (p = .7). Lower serum retinol levels were observed in RPs compared with SPs for the second and third measurements, obtained at a median of 12 and 24 months past baseline: 0.51 + 0.07 micromol/L versus 0.76 + 0.14 micromol/L (p = .3) and 0.44 + 0.09 micromol/L versus 0.64 + 0.08 micromol/L (p = .08), respectively. Median retinol levels for the third sample measurement were similar in RPs with lower viral load (LVL) and SPs (0.49 micromol/L and 0.52 micromol/L, respectively) compared with only 0.19 micromol/L in RPs with higher viral load (HVL; p = .02). A trend toward decreasing serum retinol levels and increasing HIV-1 RNA viral load was observed at the third sample measurement (p = .04). Subjects with LVL, higher serum retinol levels (> or =0.70 micromol/L), or both had more favorable rates of survival than subjects with HVL, low serum retinol levels (<0.70 micromol/L), or both. Although sample size does not permit definitive conclusions, this study demonstrates an association of high HIV load, rapid progression, and low serum retinol late but not early in disease progression.

Adult↗