Philippe Lepage

ACQUIRED IMMUNODEFICIENCY SYNDROME IN RWANDA

To evaluate acquired immunodeficiency syndrome (AIDS) in central Africa a prospective study was done in Kigali, Rwanda, where Kaposis sarcoma (KS) is endemic. During a 4 week period, 26 patients (17 males and 9 females) were diagnosed. 16 patients had opportunistic infections, associated with KS in only 2; 1 had multifocal KS alone; and 9 had clinical conditions consistent with prodromes of AIDS. All patients had severe T-cell defects characterised by cutaneous anergy, a striking decrease in the number of helper T cells, and a decreased OKT4:OKT8 ratio (mean 0.27). 21 of the 22 adult patients were living in urban centres and many of them were in the middle to upper income bracket. Most of the men were promiscuous heterosexuals and 43% of the females were prostitutes. No patient had a history of homosexuality, intravenous drug abuse, or transfusion in the previous 5 years. This study suggests that AIDS is present in central Africa as an entity probably unrelated to the well-known endemic African KS. An association of an urban environment, a relatively high income, and heterosexual promiscuity could be a risk factor for AIDS in Africa.

Natural History of Human Immunodefiency Virus Type 1 Infection in Children: A Five-Year Prospective Study in Rwanda

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.

Postnatal transmission of HIV from mother to child

2 cases of post-partum transmission of human immunodefficiency virus (HIV) from mother to infant from Kigali Rwanda are reported. All results were confirmed by western blot tests. 1) A 23-year-old woman with no history of extramarital sexual contact blood transfusions drug abuse or injections during pregnancy experienced severe bleeding during childbirth and was transfused with 2 units blood one of which had been drawn from a donor who later proved to be seropositive. The child sickened and died at 19 months of chronic diarrhea after having presented with failure to thrive generalized lymphadenopathy oral thrush and hepatomegaly moderate psychomotor delay and lobar pneumonia on chest x-ray. At 15 months post-partum the mother showed mild lymphocytosis and had antibodies to HIV. She had no dermatitis and breast-fed the child without problems until she died. 2) The 2nd case of a boy was quite similar: a postpartum transfusion from a donor who later prove to be seropositive was the most likely source of the mothers HIV infection. The child in question was still being breast fed at 15 months having begun to show symptoms of HIV infection at 5 months of age. A 30-month-old sibling was thriving and seronegative. In both cases the fathers were seronegative. Given the length of time the children had been breast fed and past studies showing the presence of HIV in breast milk as well as colostrum breast milk appears to be the most likely source of the infection in these cases. They were 2 cases out of 107 pediatric cases of AIDS and AIDS-related complex studied over 2 years. The results do not indicate a need to discourage mothers from breastfeeding but do underline the need to enforce measures to avoid contamination of banked breast milk.

Estimating the rate of mother-to-child transmission of HIV. Report of a workshop on methodological issues Ghent (Belgium) 17-20 February 1992.

PurposeIn the last 8 years, numerous cohort studies have been conducted to estimate the rate of mother-to-child transmission (MTCT) of HIV. Many of these have faced problems in data collection and analysis, making it difficult to compare transmission rates between studies. This workshop on methodological aspects of the study of MTCT of HIV-1 was held in Ghent (Belgium) in February 1992. Study selection and data extractionFourteen teams of investigators participated, representing studies from Central (five) and Eastern Africa (three), Europe (two), Haiti (one) and the United States (three). A critical evaluation of the projects was carried out, under four headings: (1) enrollment and follow-up procedures, (2) diagnostic criteria and case definitions, (3) measurement and comparison of MTCT rates and (4) determinants of transmission. Results of data analysisReported transmission rates ranged from 13 to 32% in industrialized countries and from 25 to 48% in developing countries. However, no direct comparisons could be made because methods of calculation differed from study to study. Based on this review, a common methodology was developed. Agreement was reached on definitions of HIV-related signs/symptoms, paediatric AIDS and HIV-related deaths. A classification system of children born to HIV-1-infected mothers according to their probable HIV infection status during the first 15 months of life, allowed the elaboration of a direct method of computation of the transmission rate and of an indirect method for studies with a comparison group of children born to HIV-seronegative mothers. This standardized approach was subsequently applied to selected data sets. ConclusionsThe methodology can now be applied to all studies with sufficient follow-up and comparisons made between transmission rates. This step is essential for assessing determinants of transmission and for the development of a common approach for the evaluation of interventions aimed at reducing or interrupting MTCT of HIV.

Breastfeeding with maternal antiretroviral therapy or formula feeding to prevent HIV postnatal mother-to-child transmission in Rwanda.

Objective:To assess the 9-month HIV-free survival of children with two strategies to prevent HIV mother-to-child transmission. Design:Nonrandomized interventional cohort study. Setting:Four public health centres in Rwanda. Participants:Between May 2005 and January 2007, all consenting HIV-infected pregnant women were included. Intervention:Women could choose the mode of feeding for their infant: breastfeeding with maternal HAART for 6 months or formula feeding. All received HAART from 28 weeks of gestation. Nine-month cumulative probabilities of HIV transmission and HIV-free survival were determined using the Kaplan–Meier method and compared using the log-rank test. Determinants were analysed using a Cox model analysis. Results:Of the 532 first-liveborn infants, 227 (43%) were breastfeeding and 305 (57%) were formula feeding. Overall, seven (1.3%) children were HIV-infected of whom six were infected in utero. Only one child in the breastfeeding group became infected between months 3 and 7, corresponding to a 9-month cumulative risk of postnatal infection of 0.5% [95% confidence interval (CI) 0.1–3.4%; P = 0.24] with breastfeeding. Nine-month cumulative mortality was 3.3% (95% CI 1.6–6.9%) in the breastfeeding arm group and 5.7% (95% CI 3.6–9.2%) for the formula feeding group (P = 0.20). HIV-free survival by 9 months was 95% (95% CI 91–97%) in the breastfeeding group and 94% (95% CI 91–96%) for the formula feeding group (P = 0.66), with no significant difference in the adjusted analysis (adjusted hazard ratio for breastfeeding: 1.2 (95% CI 0.5–2.9%). Conclusion:Maternal HAART while breastfeeding could be a promising alternative strategy in resource-limited countries.

Growth of human immunodeficiency type 1-infected and uninfected children : a prospective cohort study in Kigali, Rwanda, 1988 to 1993

OBJECTIVE To compare the anthropometric characteristics of children with and without HIV-1 infection. METHODS In a prospective cohort study of 218 children born to HIV-1 seropositive mothers and 218 children born to HIV-1 seronegative mothers in Kigali, Rwanda, 3 groups were compared: infected children (n = 46); uninfected children born to seropositive mothers (n = 140); and uninfected children born to seronegative mothers (n = 207). Weight, height and head circumference were measured at birth, every 3 months during the first year of life and every 6 months thereafter. The weight-for-age, height-for-age, weight-for-height and head circumference-for-age mean z scores were calculated. RESULTS The weight-for-age, height-for-age and head circumference-for-age mean z scores were lower among HIV-infected children than among uninfected ones at each time period. The reduction in the weight-for-age mean z score was the greatest between 12 and 36 months. The reduction in the height-for-age mean z score of HIV-infected children was persistently below 2 SD after 9 months of age. On the other hand the weight-for-height mean z score was not consistently lower in HIV-infected children when compared with uninfected ones. The anthropometric characteristics of uninfected children born to seropositive mothers were similar to those of children born to seronegative mothers. CONCLUSIONS In this study HIV-infected children were more frequently stunted (low height-for-age) than uninfected ones. Wasting (low weight-for-height) was not common among HIV-infected children.

COMMUNITY-ACQUIRED BACTERAEMIA IN AFRICAN CHILDREN

To examine the frequency of community acquired bacteraemia in children in Kigali, Rwanda, blood cultures were obtained from 900 consecutive febrile children (T degrees greater than or equal to 39 degrees C) seen at an outpatient clinic over the course of a year. A pathogen was isolated from 112 children (12.4%): Salmonella typhi from 47, S enteritidis from 23, S typhimurium from 13, Streptococcus pneumoniae from 14, Staphylococcus aureus from 9, and Haemophilus influenzae from 3. Salmonella species represented 74% of the isolates. The children with S typhi bacteraemia were older (mean age 75 months) than those with bacteraemia due to other organisms. Controls consisted of febrile, nonbacteraemic children without (group I) or with (group II) Plasmodium falciparum parasitaemia. Bacteraemic children were older and presented more frequently with diarrhoea, vomiting, and dehydration, but less frequently with convulsions than controls. The rate of hospital admission was higher among bacteraemic children (61%) than among group I (39%) or group II (46%) controls. The case-fatality rate was similar in the three groups (9.3% versus 2.9% and 7.3%). Community-acquired bacteraemia in Rwandese children is common and is mainly caused by Salmonella species.

A Prospective Study of the Ophthalmologic Findings in the Acquired Immune Deficiency Syndrome in Africa

A prospective study of ophthalmologic findings in 20 African patients with the acquired immunodeficiency syndrome (Group 1) and nine patients with acquired immune deficiency syndrome related complex (Group 2) disclosed that 11 patients in Group 1 and two patients in Group 2 had ocular involvement. Cotton-wool spots, Roth spots, and hemorrhages were frequent features in Group 1. In this series, unlike most others, perivasculitis occurred in five patients whereas cytomegalovirus retinitis and ocular involvement of Kaposis sarcoma were not observed. These African patients also differed from those previously described in the high proportion of women (11 of 29) and the lack of the usual risk factors (homosexuality, intravenous drug abuse, and hemophilia).

Herpes zoster in African patients: an early manifestation of HIV infection.

During a 3-month period, 131 cases of herpes zoster were diagnosed in Kigali, Rwanda. There were 46 female and 85 male patients. Mean age was 29 years (range 1-66). An unusually high proportion of patients presented with cranial and sacral nerve localisation of their cutaneous lesions. 55/131 patients (42%) had involvement of more than one dermatome. None of the patients had an underlying condition known to favour herpes zoster. 120/131 (92%) had antibodies to HIV detected by an immunoenzymatic assay (EIA) and indirect immunofluorescence. 92/125 adult patients (74%) had no sign or symptom related to HIV infection other than herpes zoster. This study suggests that herpes zoster in Central Africa is an early and readily detectable manifestation of HIV-induced immunosuppression.

Febrile Urinary Tract Infections in 0- to 3-Month-Old Infants: A Prospective Follow-Up Study

OBJECTIVE To track the clinical evolution of febrile urinary tract infection (UTI) diagnosed in 0- to 3-month-old infants and characterize uropathogen frequencies, antimicrobial resistance rates, renal abnormalities, and differences in the sexes in this age group. STUDY DESIGN We observed prospectively 46 infants identified in a cohort of 209 children with first UTI diagnosed between July 2006 and July 2008 at the age of 0 to 3 months. Renal ultrasound scanning and voiding cystourethrography examinations were performed in all infants. RESULTS Infants < 3 months old represented 21% of all children with first UTI. Of these children, 26% were female and 74% were male. Escherichia coli was isolated in 88% of cases and had a high rate of resistance to ampicillin (71%) and to trimethoprim/sulfamethoxazole (47%); 21% of children had vesicoureteral reflux, which was of low-grade in 67% of cases, with spontaneous resolution before 2 years in all cases. In infants with normal ultrasound scanning results, a low-grade vesicoureteral reflux was subsequently found in 10% of cases. CONCLUSION Infants aged 0 to 3 months represent 21% of children treated for febrile UTI. Boys represent 74% of these cases. E coli is responsible for 88% of UTIs, with a high rate of resistance to antibiotics. When ultrasound scanning examination results are normal, the risk of missing a significant renal abnormality is expected to be extremely low.