Ganapati Bhat

Lung diseases at necropsy in African children dying from respiratory illnesses: a descriptive necropsy study

BACKGROUND Accurate information about specific causes of death in African children dying of respiratory illnesses is scarce, and can only be obtained by autopsy. We undertook a study of children who died from respiratory diseases at University Teaching Hospital, Lusaka, Zambia. METHODS 137 boys (93 HIV-1-positive, 44 HIV-1-negative], and 127 girls (87 HIV-1-positive, 40 HIV-1-negative) aged between 1 month and younger than 16 years underwent autopsy restricted to the chest cavity. Outcome measures were specific lung diseases, stratified by age and HIV-1 status. FINDINGS The presence of multiple diseases was common. Acute pyogenic pneumonia (population-adjusted prevalence 39.1%, 116/264), Pneumocystis carinii pneumonia (27.5%, 58/264), tuberculosis (18.8%, 54/264), and cytomegalovirus infection (CMV, 20.2%, 43/264) were the four most common findings overall. The three most frequent findings in the HIV-1-negative group were acute pyogenic pneumonia (50%), tuberculosis (26%), and interstitial pneumonitis (18%); and in the HIV-1-positive group were acute pyogenic pneumonia (41%), P carinii pneumonia (29%), and CMV (22%). HIV-1-positive children more frequently had P carinii pneumonia (odds ratio 5.28, 95% CI 2.12-15.68, p=0.0001), CMV (7.71, 2.33-40.0, p=0.0002), and shock lung (4.15, 1.20-22.10, p=0.03) than did HIV-1-negative children. 51/58 (88%) cases of P carinii pneumonia were in children younger than 12 months, and five in children aged over 24 months. Tuberculosis was common in all age groups, irrespective of HIV-1 status. INTERPRETATION Most children dying from respiratory diseases have preventable or treatable infectious illnesses. The presence of multiple diseases might make diagnosis difficult. WHO recommendations should therefore be updated with mention of HIV-1-positive children. Improved diagnostic tests for bacterial pathogens, tuberculosis, and P carinii pneumonia are urgently needed.

Seroprevalence of Human Herpesvirus 8 among Zambian Women of Childbearing Age without Kaposi's Sarcoma (KS) and Mother-Child Pairs with KS

The seroprevalence of human herpesvirus 8 (HHV-8) among a group of Zambian women of reproductive age and among mother-child pairs in which either one of them has Kaposis sarcoma (KS) was determined. A cross-sectional group of 378 pregnant women was randomly recruited into the study, and 183 (48.4%) had HHV-8 antibodies. Among the human immunodeficiency virus (HIV)-1-infected women, 51.1% were HHV-8-seropositive, whereas of HIV-1-negative women, 47.3% were HHV-8-seropositive. In addition, 21 women index patients with KS and 5 young children index patients with KS were studied. All children with KS had mothers who were HHV-8-seropositive, while not all children whose mothers had KS were infected with HHV-8. Our study suggests that there is a high HHV-8 seroprevalence among Zambian women, and the rate is almost the same in HIV-1-positive and -negative women. This high seroprevalence may be a contributing factor toward the increased frequency of KS in this population.

Distribution of Kaposi Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 in Maternal Saliva and Breast Milk in Zambia: Implications for Transmission

BACKGROUND The seroprevalence of Kaposi sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) in sub-Saharan Africa suggests that multiple routes of transmission exist. In the present study, we examined 2 possible routes of mother-to-child transmission, through breast milk and saliva, during the first 6 months after delivery. METHODS The prevalence of HHV-8 DNA in the breast-milk cells (n=75), milk supernatant (n=56), colostrum (n=2), and saliva cells (n=65) of HHV-8-seropositive mothers who recently gave birth was examined. Polymerase chain reaction analysis was performed for the detection of HHV-8 in cross-sectional samples isolated at 2, 4, and 6 months after delivery. RESULTS None of the 75 breast-milk samples but 2 of the colostrum samples that were analyzed contained HHV-8 DNA at a limit of detection of approximately 1 HHV-8 copy/10(4) cellular genomes, whereas Epstein-Barr virus DNA and HIV-1 DNA were detected in 16 and 22 samples, respectively. Analysis of 65 saliva cell samples, which were obtained from mothers who also provided milk samples, revealed that 19 of the samples had detectable HHV-8 DNA. Viral DNA was found at all time points, but the presence of viral DNA in saliva was independent of maternal HIV-1 serostatus (chi 2=0.33; P=.57). CONCLUSIONS Our findings demonstrate the lack of HHV-8 DNA in the breast milk of seropositive mothers, and they suggest that contact with breast milk is not a likely source of horizontal transmission of virus to infants in sub-Saharan Africa.

Vertical transmission of Kaposi's sarcoma-associated herpesvirus

Little is presently known about the specific routes of transmission of Kaposis sarcoma‐associated herpesvirus (KSHV) or human herpesvirus‐8 (HHV‐8). To investigate whether this agent might be transmitted vertically from mother to infant, we conducted a study on 89 KSHV seropositive mothers and their newborn infants. Thirteen mothers (14.6%) had KSHV DNA detected in their peripheral blood mononuclear cells (PBMC). Two of 89 samples drawn at birth from infants born to KSHV seropositive mothers had KSHV DNA detectable within their PBMC. These findings suggest that KSHV can be transmitted perinatally, but infrequently. Other routes of transmission such as horizontal transmission remain the most likely means of KSHV transmission.

Seroprevalence of human immunodeficiency virus type 1 infection in zambian children with tuberculosis

Descriptions in the medical literature of human immunodeficiency virus type 1 (HIV-1) in children with tuberculosis (TB) are scanty. This study determined the seroprevalence of HIV-1 in 237 hospitalized children between the ages of 1 month and 14 years with a clinical diagnosis of TB (125 males and 112 females) and in 242 control children (149 males and 93 females). The overall HIV-1 seroprevalence rate in patients with TB was 37% (88 of 237) compared with 10.7% (26 of 242) among the control group (P < 0.00001: odds ratio 5.37, 95% confidence interval = 3.21 < 5.37 < 9.47). HIV-1 seropositivity in children with TB ranged from 53% (31 of 58) in the 12− to 18-month age group to 14% (9 of 61) in the 10− to 14-year-olds. The risk of TB attributable to HIV infection was 29%. The predominant clinical presentation in both seronegative (84.6%) and seropositive (89.7%) groups was that of pulmonary TB and there were no significant differences in clinical presentation between the two groups of patients. Only 54.8% of the patients attended follow-up clinics regularly whereas 32% were lost to follow-up within 3 months. Bacillus Calmette-Guérin vaccination coverage was 87.3% among TB patients and 90.5% in the controls. No significant differences in B. Celmette-Guérin vaccination rates between the seronegative and seropositive children were seen. Coinfection with HIV and TB in children is now one of the major public health problems in Zambian children.

Randomised study of skin-to-skin versus incubator care for rewarming low-risk hypothermic neonates

In neonates, an admission temperature of less than 36 O C is associated with or contributes to increased morbidity and mortality. 1 Skin-to-skin (STS) care prevents neonatal hypothermia 2 but has not been investigated for treatment of hypothermia. We compared STS with incubator care for rewarming low-risk infants with hypothermia. 80 consecutive low-risk hypothermic infants (clinically stable with admission weight of � 1500 g, absence of respiratory distress, no cyanosis or overt sepsis, not requiring oxygen or intravenous fluids, and no major congenital malformations), admitted to the Neonatal Intensive Care unit, at the University Teaching Hospital, Lusaka, Zambia were randomly assigned treatment with STS care by the mother (n=41) or in an incubator (n=39). The study was explained to the mother or parents and we obtained her or their consent before assignment to study groups. Incubator temperature was 35 O

Cutaneous hypersensitivity reactions due to thiacetazone in the treatment of tuberculosis in Zambian children infected with HIV-I.

Tuberculosis is one of the most common infections in Zambian adults and children infected with HIV. In Africa, cutaneous hypersensitivity reactions attributed to thiacetazone during treatment of tuberculosis in adults infected with HIV-I have been well documented. This study monitored adverse drug reactions during treatment for tuberculosis over an 18 month period (1 April 1990 to 31 October 1991) in 237 children with a clinical diagnosis of tuberculosis (125 boys and 112 girls; 88/237 (37%) infected with HIV-I) and 242 control children (149 boys and 93 girls; 26/242 (11%) infected with HIV-I). Twenty two (9%) of the 237 children with tuberculosis developed hypersensitivity skin reactions during the course of treatment. Adverse skin reactions were seen more often in children infected with HIV than in those who were not (odds ratio 11.65, 95% confidence interval 3.07 to 34.88). These represented 19 (21%) of 88 children infected with HIV and three (2%) of 149 children not infected with HIV. These skin reactions occurred after a period of treatment ranging between two and four weeks among 14 children receiving the HST (isoniazid, streptomycin, thiacetazone) regimen and eight children receiving the HSTR (isoniazid, streptomycin, thiacetazone, rifampicin) regimen. Twelve (55%) of the 22 children who reacted adversely to treatment developed the Stevens-Johnson syndrome. All 12 of these children with the Stevens-Johnson syndrome were infected with HIV. The mortality among these children who developed the Stevens-Johnson syndrome was 91% (11 of 12 died within three days of the onset of the reaction). No further reactions were observed in the 11 children who recovered from the cutaneous hypersensitivity reactions after thiacetazone was discontinued over a period of six months of further treatment of tuberculosis. The results of this study were in part responsible for the recommendations put forward by the World Health Organization to avoid the use of thiacetazone in the treatment of tuberculosis in children infected with HIV.

Postnatal Human Herpesvirus 8 and Human Immunodeficiency Virus Type 1 Infection in Mothers and Infants from Zambia

The specific route and timing of human herpesvirus (HHV) 8 infection in regions where Kaposi sarcoma is endemic are not known. HHV-8 infection and any risk factors that may be associated with HHV-8, including human immunodeficiency virus (HIV) type 1 infection, were monitored during the 12-month postdelivery period for 416 mothers and 485 infants from Lusaka, Zambia. HHV-8 incident infection rates during this period were 3.2 and 5.3 infections/100 person-years for infants and mothers, respectively. HHV-8 infection among infants was not associated with HHV-8 or HIV-1 infection in the mother. Among the HHV-8-positive infants, 2 of 12 tested were found to have HHV-8 DNA in their peripheral blood mononuclear cells at birth, which suggests that in utero infection is possible. However, most HHV-8-positive infants appeared to have acquired infection either intrapartum or postpartum. The present study indicates that transmission of HHV-8 to infants can occur early and is likely via multiple routes.

Impact of the Human Immunodeficiency Virus Type-1 on Common Pediatric Illnesses in Zambia

The seroprevalence of HIV-1 and in-patient mortality in children with common pediatric illnesses was studied. Between October 1990 and July 1991 at the Department of Paediatrics and Child Health, University Teaching Hospital (UTH), Lusaka, Zambia, mothers of all pediatric admissions were interviewed and counselled for enrollment of their children into the study. Of a total of 1323 children seen, 1266 children (600 female and 666 male) were enrolled into the study. Pneumonia (28 per cent), malaria (24 per cent), malnutrition (18 per cent), and diarrhoea (10 per cent) constituted over 80 per cent of the total admission diagnoses. Tuberculosis (5 per cent) was the fifth commonest cause of admission (61 out of 1266 children). A total of 354 out of the 1266 (28 per cent) children were found to be seropositive for HIV-1 compared to a seroprevalence rate of 9 per cent in children attending accident and emergency for traumatic injuries (P=0.001). High HIV-1 seroprevalence rates were found in children with tuberculosis (69 per cent), malnutrition (41 per cent), pneumonia (28 per cent). and diarrhoea (24 per cent). The overall mortality in hospital among HIV-seropositive children (19 per cent) was significantly higher than those who were HIV-seronegative (9 per cent) (P = < 0.0001).

Influence of partner participation on sexual risk behavior reduction among HIV-positive Zambian women.

Sexual risk behavior interventions in sub-Saharan Africa focus predominantly on individual and couples counseling. This cognitive-behavioral group intervention was adapted from an urban US context to urban Zambia. Preliminary data analyses assessed the influence of partner participation on sexual risk behavior among HIV-positive Zambian women. Female participants (n=180) attended four group intervention sessions and received sexual behavior skill training and male and female condoms; male partners (n=152) were randomly assigned to high-or low-intensity genderconcordant group intervention sessions. Sexual risk behavior, strategies, attitudes, and knowledge were assessed at baseline, 6, and 12 months. At baseline, 19% of males reported using alcohol before sex, 10% reported using alcohol to cope, and negative coping was associated with sexual risk behavior. In contrast, 1% of women reported using alcohol before sex, and 15% used alcohol as an HIV-coping strategy. Consistent barrier use was reported by 48% of women and 74% of men. After intervention, female high intensity participants reported higher rates of condom use (F=5.68, P=.02), more positive condom attitudes, safer sex intentions, and less alcohol use. These findings highlight the influence of male partners in implementation of effective risk reduction interventions.