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Biomedical subjects

Chifumbe Chintu

Publications and source records attributed to Chifumbe Chintu.

14 recordsLinked to original sources

Effect of cotrimoxazole on causes of death, hospital admissions and antibiotic use in HIV-infected children.

BACKGROUND: Cotrimoxazole prophylaxis reduces morbidity and mortality in HIV-1-infected children, but mechanisms for these benefits are unclear. METHODS: CHAP was a randomized trial comparing cotrimoxazole prophylaxis with placebo in HIV-infected children in Zambia where background bacterial resistance to cotrimoxazole is high. We compared causes of mortality and hospital admissions, and antibiotic use between randomized groups. RESULTS: Of 534 children (median age, 4.4 years; 32% 1-2 years), 186 died and 166 had one or more hospital admissions not ending in death. Cotrimoxazole prophylaxis was associated with lower mortality, both outside hospital (P = 0.01) and following hospital admission (P = 0.005). The largest excess of hospital deaths in the placebo group was from respiratory infections [22/56 (39%) placebo versus 10/35 (29%) cotrimoxazole]. By 2 years, the cumulative probability of dying in hospital from a serious bacterial infection (predominantly pneumonia) was 7% on cotrimoxazole and 12% on placebo (P = 0.08). There was a trend towards lower admission rates for serious bacterial infections in the cotrimoxazole group (19.1 per 100 child-years at risk versus 28.5 in the placebo group, P = 0.09). Despite less total follow-up due to higher mortality, more antibiotics (particularly penicillin) were prescribed in the placebo group in year one [6083 compared to 4972 days in the cotrimoxazole group (P = 0.05)]. CONCLUSIONS: Cotrimoxazole prophylaxis appears to mainly reduce death and hospital admissions from respiratory infections, supported further by lower rates of antibiotic prescribing. As such infections occur at high CD4 cell counts and are common in Africa, the role of continuing cotrimoxazole prophylaxis after starting antiretroviral therapy requires investigation.

Anti-Infective Agents↗

Determinants of survival without antiretroviral therapy after infancy in HIV-1-infected Zambian children in the CHAP Trial.

BACKGROUND: There are few data on predictors of HIV progression in untreated children in resource-limited settings. METHODS: Children with HIV Antibiotic Prophylaxis (CHAP) was a randomized trial comparing cotrimoxazole prophylaxis with placebo in HIV-infected Zambian children. The prognostic value of baseline characteristics was investigated using Cox models. RESULTS: Five hundred fourteen children aged 1 to 14 (median 5.5) years contributed 607 years follow-up (maximum 2.6 years). Half were boys, and in 67%, the mother was the primary carer; at baseline, median CD4 percentage was 11% and weight was less than third percentile in 67%. One hundred sixty-five children died (27.2 per 100 years at risk; 95% confidence interval 23.3-31.6). Low weight-for-age, CD4 percentage, hemoglobin, mother as primary carer, current malnutrition, and previous hospital admissions for respiratory tract infections or recurrent severe bacterial infections were independent predictors of poorer survival, whereas oral candidiasis predicted poorer survival only when baseline CD4 percentage was not considered. Mortality rates per 100 child years of 44.5 (37.2-53.2), 14.7 (10.9-19.8), and 2.3 (0.3-16.7) were associated with new World Health Organization stages 4, 3, and 1/2, respectively, applied retrospectively; very low weight-for-age was the only staging feature for 42% of stage 4 children. CONCLUSIONS: Malnutrition and hospitalizations for respiratory/bacterial infections predict mortality independent of immunosuppression, suggesting that they capture HIV- and non-HIV-related mortality, whereas oral candidiasis is a proxy for immunosuppression.

AIDS-Related Opportunistic Infections↗

Factors influencing breast milk HIV RNA viral load among Zambian women.

In a longitudinal cohort study we investigated factors contributing to breast milk HIV RNA viral load among lactating women in Lusaka, Zambia. Detailed data from 135 HIV-infected women were collected by questionnaires concerning postpartum maternal and infant health and infant feeding practice. Maternal blood was collected during pregnancy and at 6 weeks postpartum. Milk samples collected from each breast at 10 days and 6 weeks postpartum plus a subset collected at other time points were analyzed for HIV RNA viral load. Increased milk viral load was associated in univariate analyses with maternal symptoms of poor health, raised plasma alpha(1)-acid glycoprotein (AGP) at week 6, raised milk sodium/potassium (Na/K) ratio, postpartum need for antibiotics, preterm delivery, and low birth weight infants. In a multiple regression 49% of variability in mean milk viral load was explained by milk Na/K ratio and need for antibiotics, with borderline contributions from plasma AGP and plasma viral load. Maternal blood hemoglobin or receipt of iron supplements and infant feeding variables such as changing the infant's diet by moving from exclusive to nonexclusive breastfeeding or adding solid foods were not associated with milk viral load. Thus maternal health was the main factor contributing to milk viral load. The lack of effect of feeding practices on milk viral load and the previously determined association of poor maternal health with reduced duration of exclusive breastfeeding in this cohort suggest the relation between exclusive breastfeeding and decreased HIV transmission may be secondary to poor maternal health.

Adult↗

Risk factors for subclinical mastitis among HIV-infected and uninfected women in Lusaka, Zambia.

Subclinical mastitis, defined as raised milk sodium/potassium (Na/K) ratio, is associated with poor infant growth and, among HIV-infected women, with increased milk HIV viral load. We conducted a longitudinal cohort study in Lusaka, Zambia, in order to investigate the relative importance of several potential causes of subclinical mastitis: maternal infection, micronutrient deficiencies and poor lactation practice. Women (198 HIV-infected, 189 HIV-uninfected) were recruited at 34 weeks' gestation and followed up to 16 weeks postpartum for collection of information on their health, their infant's health, infant growth and infant feeding practices. Milk samples were collected from each breast at 11 postpartum visits and blood at recruitment and 6 weeks postpartum. The geometric mean milk Na/K ratio and the proportion of women with Na/K ratio > 1.0 in one or both breasts were significantly higher among HIV-infected than among uninfected women. Other factors associated with the higher mean Na/K ratio in univariable analyses were primiparity, high maternal alpha(1)-acid glycoprotein (AGP) at 6 weeks, maternal overall morbidity and specific breast symptoms, preterm delivery, low infant weight or length, infant thrush and non-exclusive breast feeding. In multivariable analyses, primiparity, preterm delivery, breast symptoms, HIV status and raised AGP were associated with the raised Na/K ratio. Thus the main factors associated with subclinical mastitis that are amenable to intervention are poor maternal overall health and breast health. The impact of improved postpartum health care, especially management of maternal infections and especially in primiparous women, on the prevalence of subclinical mastitis and its consequences requires investigation.

Adult↗

Factors affecting the duration of exclusive breastfeeding among HIV-infected and -uninfected women in Lusaka, Zambia.

Exclusive breastfeeding (EBF) is optimal for infant health and is associated with decreased risk of mother-to-child HIV transmission compared with mixed feeding of breast milk and other foods. To investigate why many women stop EBF before the recommended 6 months, maternal and infant health and infant-feeding data were collected from 177 HIV-infected and 177-uninfected Zambian women regularly from 34 weeks gestation to 16 weeks postpartum. Despite strong support for good breastfeeding practice, only 37% of women were still EBF at week 16. Factors significantly associated with shorter duration of EBF were primiparity, maternal systemic illness, and infant length at 6 weeks. The results suggest that the association of EBF with lower rates of mother-to-child HIV transmission may not be causal but may be secondary to the reduced duration of EBF associated with poor maternal or infant health. Programs supporting EBF should include support for maternal health.

Adult↗

Improved nutritional recovery on an elemental diet in Zambian children with persistent diarrhoea and malnutrition.

The persistent diarrhoea-malnutrition syndrome (PDM) remains a leading cause of morbidity and mortality in hospitals in resource-poor countries. In view of the benefits of elemental or oligomeric feeds in inflammatory bowel diseases, we performed a randomized controlled trial of an exclusive diet of amino acid-based elemental feed (AAF) compared with standard nutritional rehabilitation (based on skimmed milk and then soya) for PDM. Treatment was given for 4 weeks in the malnutrition ward of the University Teaching Hospital, Lusaka, in a single-blind study. Intestinal and systemic infections were treated with routine therapies. The main outcome measures were weight gain, recovery from diarrhoea, and mortality. Two hundred children (106 HIV seropositive, 90 HIV seronegative) were randomized; 155 children completed therapy, 39 died, and six were lost to follow-up. At randomization, they were severely malnourished: median baseline weight-for-age z-score was -4.0 (interquartile range, IQR -4.4, -3.5); 9 per cent were underweight, 23 per cent had marasmus, 47 per cent had kwashiorkor, and 21 per cent had marasmic-kwashiorkor. Weight gain was greater in the AAF group (median gain in weight-for-age z-score was 1.23, IQR 0.89-1.57) compared with the control group (0.87, IQR 0.47-1.25; p=0.002), although calorie intakes were higher in the control group. The increase in haemoglobin concentration was also greater in the AAF group (0.8 g/dl, IQR 0-1.8) than in the control group (0.3, IQR -0.6, -1.6; p=0.04). Diarrhoea frequency and global recovery scores improved equally in both treatment groups and mortality did not differ. A diet of reduced molecular complexity was associated with significantly improved weight gain.

Anthropometry↗

Congenital trypanosomiasis.

The last successfully treated case of congenital trypanosomiasis in Zambia was in October 1978, with detailed analysis of immunoglobulins, illustrating the waning of blood and serum levels of IgA, IgG, and IgM during treatment, up to 99 days after treatment. Twenty-five years later, we report on a case of congenital trypanosomiasis. The disease is now rare and can be missed or dismissed as retroviral disease, particularly in adults. The main unusual symptoms were the prolonged intermittent convulsions in an otherwise well infant. Management of the disease is now more interdisciplinary, resources for laboratory support are fewer, lumbar puncture is more relevant, and antitrypanosomal drugs are more difficult to obtain. The mother died within one week of hospitalization and the infant initially responded to three doses of suramin and 3 weeks of melsopropol. Convulsions ceased during the second round of melsopropol. Unfortunately, the infant died of nosocomial infection.

Adult↗

Whole blood versus plasma spots for measurement of HIV-1 viral load in HIV-infected African patients.

The increasing availability of antiretroviral drugs to HIV-infected populations in developing countries highlights the need to develop field-friendly practical methods for HIV-1 viral load measurements to monitor the effects of treatment. We compared use of whole-blood spots versus plasma dried on filter paper to quantify HIV-1 viral load in 51 African patients with HIV-1. The mean log10 HIV-1 viral loads were 4.22 for dried plasma spots (DPS) and 4.20 for dried whole-blood spots (DBS). The difference between the pairs of log10 viral load for DPS and DBS were significantly correlated with their mean (Spearman's r=0.31, p=0.03). This correlation between the difference and mean of viral load was no longer evident for values of log10 DPS that were less than 5 (r=0.01, p=0.93). For the 38 paired values with log10DPS of less than 5, the mean difference (log10DPS-log10DBS) was -0.04 (SD 0.29). Dried whole blood stored on filter paper at room temperature shows potential as a field-friendly alternative to plasma for measurement of HIV-1 viral load.

Adult↗

Use of dried whole blood spots to measure CD4+ lymphocyte counts in HIV-1-infected patients.

As antiretroviral drugs become widely available in developing countries, practical, field-friendly, and cheap methods of measuring CD4+ lymphocyte counts need to be developed. We tested use of whole blood spots dried on filter paper to measure CD4+ lymphocyte counts. We obtained blood from 42 HIV-1-infected patients from Zambia. We dried blood spots on filter paper and measured CD4+ lymphocyte counts with an established commercial enzyme immunoassay. We compared these measurements with those obtained from matched liquid whole-blood samples analysed with standard flow cytometry. Results of the filter-paper method accorded well with flow cytometry CD4 counts greater than 200 cells/microL (mean difference 13.6 [SD 52.4]). Dried whole blood stored on filter paper could be developed into a field-friendly alternative for CD4+ lymphocyte count measurements.

Blood Specimen Collection↗

Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial.

BACKGROUND: Mortality rates of HIV-infected patients treated for tuberculosis remain high. This study aimed to assess the effect on mortality of immunotherapy with single-dose SRL172 added to standard antituberculosis chemotherapy in such patients. METHODS: The double-blind trial enrolled 1229 patients aged 18-60 years, who had never received antiretroviral treatment and who presented with newly diagnosed, sputum-smear-positive pulmonary tuberculosis to referral centres in Lusaka, Zambia, and Karonga, Malawi. Both HIV-positive and HIV-negative patients were enrolled, to avoid stigmatisation. Participants were randomly assigned a single injection of SRL172 or matching placebo within 2 weeks of starting 8 months of antituberculosis chemotherapy and followed up for at least 12 months. The primary endpoint was time to death in the HIV-infected population. Analyses were based on 760 HIV-positive patients after exclusion of 84 patients with errors in storage of the injection, no bacteriological confirmation, or no HIV result. FINDINGS: Of 760 HIV-infected patients, 374 received SRL172 and 386 received placebo. SRL172 did not cause any serious adverse events. The follow-up rate was 88% at 12 months in both groups. Of the HIV-positive patients, 109 (19.5 per 100 person-years) of 372 assigned SRL172 and 107 (19.3 per 100 person-years) of 386 assigned placebo died. In the Cox's regression analysis, stratified by centre, the hazard ratio of deaths (SRL172/placebo) was 1.03 (95% CI 0.79-1.35). There was no evidence of benefit to the group assigned SRL172. INTERPRETATION: Immunotherapy with single-dose SRL172 as an adjunct to standard antituberculosis treatment in HIV-positive adults with pulmonary tuberculosis had no significant effect on survival or bacteriological outcome, though the treatment was safe and well tolerated.

AIDS-Related Opportunistic Infections↗

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.

Adolescent↗

Identification of Pneumocystis carinii DNA in oropharyngeal mouth washes from AIDS children dying of respiratory illnesses.

Polymerase chain reaction (PCR) using Pneumocystis carinii-specific primers pAZ 102-H(5'-GTGTACGTTGCAAAGTACTC-3') and pAZ 102-E(5'-GATGGCTGTTTCCAAGCCCA-3') was performed on oropharyngeal washes obtained at autopsy from 22 AIDS children with histologically confirmed P. carinii pneumonia (PCP), and 48 control AIDS children who died from other infections. Fifteen of 22 (68%) PCP samples and none of 48 (0%) control samples had detectable P. carinii DNA (sensitivity 68%; specificity 100%; positive predictive value 100%; negative predictive value 87%). This method requires further validation in clinical practice.

Acquired Immunodeficiency Syndrome↗

Identification of Pneumocystis carinii DNA by polymerase chain reaction in necropsy lung samples from children dying of respiratory tract illnesses.

Polymerase chain reaction for Pneumocystis carinii DNA was performed on necropsy lung samples from children by means of P carinii -specific primers.P carinii DNA was identified in 22 of 22 (100%) samples with histologically proven P carinii pneumonia and 13 of 75 (17%) with non-P carinii pneumonia respiratory illness (sensitivity, 100%; specificity, 83%). The low specificity precludes the use of polymerase chain reaction as an alternative to histopathologic diagnosis.

Autopsy↗