Poor association between 13-valent pneumococcal conjugate vaccine-induced serum and mucosal antibody responses with experimental Streptococcus pneumoniae serotype 6B colonisation.

BACKGROUND: Pneumococcal carriage is the primary reservoir for transmissionand a prerequisite for invasive pneumococcal disease. Pneumococcal Conjugate Vaccine 13 (PCV13) showed a 62% efficacy in protection against experimental Streptococcus pneumoniae serotype 6B (Spn6B) carriage in a controlled human infection model (CHIM) of healthy Malawian adults. We, therefore, measured humoral responses to experimental challenge and PCV-13 vaccination and determined the association with protection against pneumococcal carriage. METHODS: We vaccinated 204 young, healthy Malawian adults with PCV13 or placebo and nasally inoculated them with Spn6B at least four weeks post-vaccination to establish carriage. We collected peripheral blood and nasal lining fluid at baseline, 4 weeks post-vaccination (7 days pre-inoculation), 2, 7, 14 and > 1 year post-inoculation. We measured the concentration of anti-serotype 6B Capsular Polysaccharide (CPS) Immunoglobulin G (IgG) and IgA antibodies in serum and nasal lining fluid using the World Health Organization (WHO) standardised enzyme-linked immunosorbent assay (ELISA). RESULTS: PCV13-vaccinated adults had higher serum IgG and nasal IgG/IgA anti-Spn6B CPS-specific binding antibodies than placebo recipients 4 to 6 weeks post-vaccination, which persisted for at least a year after vaccination. Nasal challenge with Spn6B did not significantly alter serum or nasal anti-CPS IgG binding antibody titers with or without experimental pneumococcal carriage. Pre-challenge titers of PCV13-induced serum IgG and nasal IgG/IgA anti-Spn6B CPS binding antibodies did not significantly differ between those that got experimentally colonised by Spn6B compared to those that did not. CONCLUSION: This study demonstrates that despite high PCV13 efficacy against experimental Spn6B carriage in young, healthy Malawian adults, robust vaccine-induced systemic and mucosal anti-Spn6B CPS binding antibodies did not directly relate to protection.

Change in sexual behaviour and decline in HIV infection among young pregnant women in urban Uganda.

OBJECTIVE: To describe sexual behaviour that may partly explain a decline in HIV seroprevalence in pregnant women in urban settings in Uganda, East Africa. SETTINGS: Two major urban districts in Uganda. METHODS: Repeated population-based behavioural surveys in 1989 and 1995, and repeated HIV serological surveys in consecutive pregnant women attending antenatal clinics from 1989 to 1995. RESULTS: During the study period, a 2-year delay in the onset of sexual intercourse among youths aged 15-24 years and a 9% decrease in casual sex in the past year in male youths aged 15-24 years were reported. Men and women reported a 40% and 30% increase in experience of condom use, respectively. In the same study area, over the same period, there was an overall 40% decline in the rates of HIV seroprevalence among pregnant women attending antenatal clinics. It can be hypothesized that the observed declining trends in HIV correspond to a change in sexual behaviour and condom use, especially among youths. CONCLUSIONS: This is the first report of a change over a period of 6 years in male and female sexual behaviour, assessed at the population level, that may partly explain the observed decline in HIV seroprevalence in young pregnant women in urban Uganda. This result should encourage AIDS control programmes to pursue their prevention activities.

PIP: Repeated serologic surveys conducted in consecutive pregnant women attending antenatal clinics in three urban sites--Nsambya, Rubaga, and Jinja--in Uganda in 1989-95 documented substantial declines (27-47%) in HIV prevalence. Multiple population-based behavioral surveys conducted in urban Uganda in 1989 and 1995 suggest this decline in HIV prevalence among pregnant women may be a result of three key changes in sexual practices: a 2-year delay in the onset of sexual intercourse among young people 15-24 years of age, a 9% decrease in the practice of casual sex among males 15-24 years old, and increases in the experience of condom use of 40% among males and 30% among females. Proportions of male and female youth reporting they had never had sexual intercourse increased from 31% and 26%, respectively, in 1989 to 56% and 46%, respectively, in 1995. The prevalence among men in the past year of sex outside relationships that had lasted more than 12 months declined from 22.6% in 1989 to 18.1% in 1995. The proportion of men and women who reported exchanging sex for money dropped by almost 50%. Finally, the proportion of sexually active respondents who reported ever-use of condoms increased from 15.4% to 55.2% among men and from 5.8% to 38.7% among women from 1989 to 1995. In two of the three urban areas, the decline in HIV prevalence was sharpest among pregnant women in the youngest age group (15-24 years), suggesting a true decrease. The finding of substantial changes in the sexual behavior of urban Ugandan youth confirms the efficacy of AIDS prevention and control interventions.

Participatory evaluation of counselling, medical and social services of The AIDS Support Organization (TASO) in Uganda.

The AIDS Support Organization (TASO) is an indigenous non-governmental organization (NGO) of HIV-infected and affected people in Uganda. TASO provides counselling, social support, medical and nursing care for opportunistic infections at 7 centres affiliated to district hospitals in Uganda. Between 1993 and 1994, the services provided by TASO were evaluated through a participatory approach between staff and clients. TASO counselling services helped clients and their families to cope with HIV and AIDS, with 90.4% of clients revealing their serostatus, and 57.2% reporting consistent use of condoms in the past 3 months. TASO was also the main source of medical care for clients with opportunistic infections in the last 6 months (63.8%). As a result of counselling, over half of the clients (56.9%) made plans for the future and 51.3% wished to make wills. There was a high level of acceptance of people living with HIV/AIDS (PWAs) by families (79%) and the community (76%). Care was provided to PWAs at home mainly by women (86.2%). TASO has demonstrated that individuals and their families are able to live positively with HIV/AIDS. Through counselling, medical care and material support to clients and their families, TASO has effected change in people's attitudes, knowledge and lifestyles. In particular, TASO has demonstrated a strong capacity to overcome four problems that haunt AIDS care in most places: (1) revealing one's HIV-serostatus to relevant others; (2) accepting PWAs in family and community; (3) seeking early treatment; and (4) combining prevention and care. In general, TASO has shown that specialized services to meet AIDS care needs can be added to existing health services at district levels. As a result of the participatory evaluation, a well-accepted monitoring system was established.

PIP: The AIDS Support Organization (TASO) is an indigenous nongovernmental organization of HIV-infected and affected people in Uganda. The organization provides counseling, social support, and medical and nursing care for opportunistic infections at seven centers affiliated with district hospitals in Uganda. TASO's services were evaluated during 1993-94 via a participatory approach involving staff and clients. The organization's counseling services helped clients and their families to cope with HIV and AIDS, with 90.4% of clients revealing their serostatus, and 57.2% reporting the consistent use of condoms during the preceding 3 months. TASO was the main source of medical care for clients with opportunistic infections during the preceding 6 months. As a result of counseling, 56.9% of clients made plans for the future and 51.3% wished to make wills. The evaluation further found a high level of acceptance of people with HIV/AIDS (PWA) by families (79%) and the community (76%). Women provided 86.2% of in-home care to PWA. TASO's experience demonstrates that individuals and their families can live positively with HIV/AIDS and that specialized AIDS care services can be readily added to existing health services at the district level.

Human immunodeficiency virus infection dynamics in east Africa deduced from surveillance data.

Knowledge of human immunodeficiency virus type 1 (HIV) incidence patterns in East African HIV epidemics like that in Uganda is fundamental for guiding interventions and forecasting the future course of the pandemic, yet they are difficult to determine from surveillance data. The authors deduce hypotheses of HIV incidence dynamics from birth cohort analyses of Ugandan acquired immunodeficiency syndrome (AIDS) incidence from 1987 to 1992 and from the age and sex distribution of sexually transmitted disease: an age dependency for HIV risk; a period effect of varying HIV incidence growth; and a replenishment of HIV-susceptible populations through demographic renewal. The hypotheses are tested by incorporating them into a model that generates patterns of HIV incidence, prevalence, and AIDS cases that are consistent with empiric data. When applied to Uganda, the modeled HIV incidence is characterized by a short temporal concentration of high incidence, followed by a decline, stabilization, and concentration in younger ages. The ensuing HIV dynamics result in a rapid build-up and subsequent stabilization of prevalence and mortality in years 10 and 13, respectively, after epidemic onset. When this model is used to forecast scenarios from 1980 to 2000, HIV prevalence declines in some populations, which is different from earlier scenarios. The techniques presented provide an empiric basis to better direct interventions, forecast epidemic impacts, and evaluate determinants of changing incidence and prevalence patterns.

PIP: Knowledge of HIV incidence patterns helps to guide interventions and forecast the future course of the HIV/AIDS pandemic. The authors deduce hypotheses of HIV incidence dynamics from birth cohort analyses of Ugandan AIDS incidence during 1987-92 and from the age and sex distribution of sexually transmitted disease. The hypotheses are then tested by incorporating them into a model which generates patterns of HIV incidence, prevalence, and AIDS cases consistent with empirical data. Applied to Uganda, the modeled HIV incidence is characterized by a short temporal concentration of high incidence, followed by a decline, stabilization, and concentration in younger ages. A rapid build-up is then envisaged followed by a stabilization of prevalence and mortality in years 10 and 13, respectively, after epidemic onset. When the model is used to forecast scenarios over the period 1980-2000, HIV prevalence declines in some populations, different from earlier scenarios. The techniques presented in this paper provide an empirical basis upon which to better direct interventions, forecast epidemic impacts, and evaluate the determinants of changing incidence and prevalence patterns.

Individual counseling of patients with sexually transmitted diseases. A way to improve partner notification in a Zambian setting?

BACKGROUND: Sexually transmitted diseases (STD) are a major health problem in Zambia. Partner notification, which is a recommended strategy to decrease STD, must be improved. GOAL: To assess whether individual counseling of patients with STD, combined with contact slip(s), had any impact on the proportion of sex partners traced in an urban setting in Zambia. STUDY DESIGN: A randomized trial comprised of 94 women and 302 men with STD. RESULTS: Women and men in the intervention group informed more partners than did those in the control group. In the intervention group, 1.8 partners per man was treated compared to 1.2 in the control group (P < 0.001). There was no difference between the two groups of women. There was a gradual decline from numbers of partners informed to numbers of partners treated according to the patient to number of contact slips filed. CONCLUSIONS: Individual counseling of men with STD improved partner notification.

PIP: In Lusaka, Zambia at an urban health center, researchers randomly allocated 302 male sexually transmitted disease (STD) patients and 94 female STD patients to receive or not receive individual counseling combined with written information to sex partners (i.e., contact slips). They aimed to determine whether or not this intervention improved partner notification. This study was conducted during October 1992-March 1993. The most common STD for men was chancroid, followed by gonorrhea and syphilis. For women, it was syphilis, followed by gonorrhea. Men and women in the intervention group were more likely to bring at least one sex partner to the clinic than those in the control group (100% vs. 93% and 72% vs. 56%, respectively). Men in the intervention group brought more partners from the last three months to the clinic than those in the control group (1.8 vs. 1.2; p 0.001), while women in both groups brought the same number of partners (0.7). In the intervention group, more partners of the men received treatment based on contact slips than partners of the women (1.6 vs. 0.4). For both sexes, based on the number of contact slips filed, the numbers of partners informed fell gradually with the numbers of partners treated. Men in the intervention group were less likely than those in the control group not to tell all partners from the last three months to come for treatment (19% vs. 48%). Among controls, the reasons were health staff failed to tell them to bring more than one partner and the men could not afford the medicines for their partners. Among cases, the leading reason was that the partners were unknown or out of town. Quarrels that prevented partners from seeking treatment occurred equally in both groups of women. They occurred more often among male cases than male controls, however (p = 0.0008). Yet partners of male controls who had experienced quarrels were less likely to seek treatment than those of male cases (p = 0.0015). The quarrels-related findings suggest the need for counseling to emphasize partners' emotional reactions and how to deal with these reactions. Overall findings show that individual counseling of men improved STD partner notification.

Preventive chemotherapy for HIV-associated tuberculosis in Uganda: an operational assessment at a voluntary counselling and testing centre.

OBJECTIVE: To assess the operational aspects of isoniazid preventive chemotherapy (IPT) for tuberculosis in persons dually infected with HIV and Mycobacterium tuberculosis identified at an independent HIV voluntary counselling and testing centre in Kampala, Uganda. DESIGN: HIV-infected persons were counselled, had active tuberculosis excluded by medical examination, and were offered purified protein derivative (PPD) skin testing. PPD-positive persons were offered isoniazid 300 mg daily for 6 months. Drugs were supplied, and toxicity and compliance were assessed monthly. Utilization of service, cost, and sustainability were also assessed. RESULTS: Between 14 June 1991 and 30 September 1992, 9862 persons tested HIV-positive. Of 5594 HIV-infected clients who returned to collect test results, only 1524 (27%) were enrolled. Of those, 1344 were tuberculin-tested (88%); 180 were not tested because of active tuberculosis, serious illnesses, refusal, and other reasons. Of the 1344, 250 (19%) did not return for test reading and 515 were negative (47% of tests read). Of 579 tuberculin-positive persons, 59 (10%) were excluded from preventive chemotherapy because of tuberculosis and other respiratory illnesses. Of 520 persons given isoniazid, 62% collected at least 80% of their drug supplies. No major toxicity was observed. One case of tuberculosis occurred in the first month of treatment. Cost of HIV counselling and testing was US $18.54 per person and cost of follow-up counselling and social support was US $7.89. CONCLUSIONS: Important factors were identified which caused attrition, such as limited motivation by counsellors to discuss tuberculosis issues during HIV pre- and post-test counselling, insufficient availability of medical screening, shifting of sites to collect pills, and frequent tuberculin-negative tests. Active tuberculosis among 6% of persons screened suggests that voluntary counselling and testing sites may be important for tuberculosis case finding and underscores the need to exclude tuberculosis carefully before starting IPT. In developing countries, further studies assessing the feasibility of IPT within tuberculosis and HIV/AIDS programme conditions are needed. Cost-effectiveness of IPT, compared with passive case finding, and its sustainability should be assessed before national policies are established.

PIP: Those infected with human immunodeficiency virus (HIV) have a 5-10% risk per year of developing active tuberculosis, and this disease may accelerate the clinical course of HIV infection. Thus, a study was conducted in Uganda to assess the cost-effectiveness and acceptability of isoniazid preventive chemotherapy (IPT) for patients dually diagnosed with HIV and Mycobacterium tuberculosis. Of the 1344 HIV-infected patients at an independent HIV testing and counseling center in Kampala who were initially screened for participation in this study, 6% had signs of active tuberculosis. Selected for participation in the study were 520 subjects with no signs of active tuberculosis. Of these, 322 (62%) were considered compliant with the treatment regimen on the basis of their appearance for all scheduled appointments for pill distribution. One case of active tuberculosis occurred during the first month of IPT and most likely represented a case that went undetected in the screening process. No treatment-associated toxicity was reported. The cost of the HIV testing and counseling was US$18.54 per patient; that of follow-up counseling and support was $7.89. When administrative costs for the study were included in the calculation, the cost of IPT increased to $60.19 per person. Although reactivation of tuberculosis may have been prevented in up to 62% of subjects who received IPT, numerous factors mitigate against the routine implementation of such a treatment program, most notably its high cost and a shortage of voluntary HIV centers in developing countries. Needed are studies that evaluate the long-term community health, social, and economic benefits of such a program as well as further investigations of the impact of tuberculosis on the pace of progression from HIV to acquired immunodeficiency syndrome (AIDS).

The impact of human immunodeficiency virus on response to treatment and recurrence rate in patients treated for tuberculosis: two-year follow-up of a cohort in Lusaka, Zambia.

To examine the effect of HIV on response to treatment and recurrence rate in patients with tuberculosis (TB), we have followed 239 previously untreated, adult, TB patients in a prospective cohort study in Lusaka, Zambia. One hundred and seventy-four (73%) were HIV-1 antibody positive. Patients with sputum smear positive, miliary, or meningeal TB were prescribed 2 months daily streptomycin, thiacetazone, isoniazid, rifampicin, pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. Thirty-five per cent of HIV-positive (HIV+ve) and 9% of HIV-negative (HIV-ve) patients were known to have died before the scheduled end of treatment. Surviving HIV+ve patients showed weight gain and improvement in symptoms and laboratory and radiological findings similar to HIV-ve patients. The risk of cutaneous drug reaction was 17% (95% CI: 12-25%) in HIV+ve, and 4% (1-13%) in HIV-ve patients. Severe rashes were attributed to thiacetazone. Recurrence of active TB was examined among 64 HIV+ve and 37 HIV-ve patients who successfully completed treatment, with mean follow-up after the end of treatment of 13.5 and 16.8 months, respectively. The rate of recurrence was 22/100 person years (pyr) for HIV+ve patients and 6/100 pyr for HIV-ve patients, giving a recurrence rate ratio of 4.0 (95% CI 1.2-13.8, P = 0.03).

PIP: In 1989, researchers followed 239 newly diagnosed adult patients with tuberculosis (TB), never previously treated for TB, for two years to examine the response to TB treatment among patients with and without HIV infection and the TB recurrence rate. They were patients in the medical wards and the chest clinic outpatients' department of the University Teaching Hospital in Lusaka, Zambia. 174 (73%) tested positive for HIV. HIV-positive patients were more likely than HIV-negative patients to have extrapulmonary and both pulmonary and extrapulmonary TB (35% and 26% for both, respectively vs. 17% and 12%, respectively; p 0.001). They were less likely to have positive sputum tests than HIV-negative patients (36% vs. 57% for smear; p = 0.005 and 39% vs. 55% for culture; p = 0.03). HIV-positive patients were more likely to receive standard TB therapy (62% vs. 37%), while HIV-negative patients were more likely to receive short course therapy (62% vs. 37%; p = 0.001). HIV-positive patients were more likely than HIV-negative patients to die before completion of treatment (35% vs. 9%). Surviving HIV-positive patients gained weight and experienced improvement in symptoms at the same rate as did surviving HIV-negative patients. They also had similar laboratory and radiological findings. HIV-positive patients had a higher risk of cutaneous drug reaction than HIV-negative patients (17% vs. 4%; hazard ratio = 5.1; p = 0.03). One HIV-positive patient with a rash died. Thiacetazone was responsible for the rashes. Among the HIV-positive and HIV-negative patients who successfully completed treatment, the active TB recurrence rate was greatest for HIV-positive patients (22 vs. 6/100 person years; rate ratio = 4; p = 0.03). Yet, all but one of the HIV-positive cases with recurrent TB responded well to TB treatment. High recurrence rates pose renewed potential sources of infection and a high cost of renewed treatment.

Tuberculin sensitivity and HIV-1 status of patients attending a sexually transmitted diseases clinic in Lusaka, Zambia: a cross-sectional study.

A cross-sectional study to estimate the prevalence of latent tuberculosis (TB) in a group of Zambians at high risk of human immunodeficiency virus type 1 (HIV-1) infection and to examine the effect of HIV-1 infection on the tuberculin response was conducted in the University Teaching Hospital in Lusaka, Zambia during July to September 1990. Patients were selected from those presenting to the out-patient clinic for first referral with either sexually transmitted or skin disease. 268 adults were included in the study; 158 (59%; 95% confidence interval [CI] = 53-65%) were HIV-1 antibody positive. Of 82 HIV-1 negative participants who returned for Mantoux skin test reading, 51 (62%; 95% CI = 57-67%) had a positive test reaction (diameter > or = 10 mm) after receiving 2 units of RT-23 tuberculin. Of 106 HIV-1 positive participants who returned, only 32 (30%; 95% CI = 26-34%) had a diameter > or = 10 mm. Nine (28%) of the HIV-1 positive and Mantoux positive participants had large reactions > or = 30 mm, compared to 4 (8%) of the HIV-1 negative, Mantoux positive participants (P = 0.03). Results in the HIV-1 negative group indicated a prevalence of latent TB of 62% in this population. HIV-1 infection was associated with a much higher frequency of negative response to tuberculin and with a few large skin test responses. Thus, in populations where HIV seropositivity is high, Mantoux skin tests cannot be used to assess those with latent TB who might benefit from chemoprophylaxis.

PIP: A cross-sectional study of the Mantoux response and HIV-1 status of a sample of patients with sexually transmitted diseases and skin diseases in Lusaka, Zambia, sought to estimate the prevalence of latent tuberculous infection. The sample was selected from patients attending the sexually transmitted diseases/dermatology section at the University Teaching Hospital, Lusaka, Zambia, between July and September 1990. A questionnaire regarding socioeconomic factors, history of TB, contact with TB, location and documentation of bacillus Calmette-Guerin (BCG) scar(s) and history of BCG vaccination was completed, and a physical examination for acquired immune deficiency syndrome (AIDS) was carried out. The Mantoux result was recorded as the average diameter of induration, measured in 2 perpendicular directions by the pen and palpation method. A total of 158 patients (59%) were HIV-1 positive. Of the 66 women who took part, 46 (70%) were HIV-1 positive; of the 201 men, 112 (56%) were HIV-1 positive (p = 0.06). 232 patients had sexually transmitted diseases, the commonest being genital ulceration; 123/231 (53%) were HIV-1 positive. The remaining 36 patients had skin diseases, the commonest being herpes zoster; 32/36 (89%) were HIV-1 positive. Of the 267 patients remaining in the study, 193 (72%) returned to have their Mantoux test read, 188 within 48-72 h. 106 (67%) HIV-1 positive patients and 82 (75%) HIV-1 negative patients returned. Of the 82 HIV-1 negative patients, 51 (62%) had a Mantoux reaction or= 10 mm; 55 (67%) had a reaction or= 5 mm. Of the 106 HIV-1 positive patients, only 32 (30%) had a Mantoux reaction or= 10 mm; 35 (33%) had a response or= 5 mm. Comparing HIV-1 negative and HIV-1 positive participants gave a significant odds ratio of 3.85 for a Mantoux response or= 10 mm. Among the individuals with a Mantoux reaction or= 10 mm, 9/32 (28%) of HIV-1 positive participants had a megareaction or= 30 mm, while megareactions occurred in 4/51 (8%) of HIV-1 negative participants (odds ratio 4.6).

The impact of human immunodeficiency virus on mortality of patients treated for tuberculosis in a cohort study in Zambia.

We have examined the impact of human immunodeficiency virus (HIV) on mortality of patients treated for tuberculosis in a prospective study in Lusaka, Zambia. Patients with sputum smear-positive, miliary, or meningeal tuberculosis were prescribed 2 months' daily streptomycin, thiacetazone, isoniazid, rifampicin, and pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. 239 patients (65 HIV-negative and 174 HIV-positive) were followed to 2 years from start of treatment. The crude mortality rate ratio for HIV-positive compared with HIV-negative patients over 2 years was 5.00 (95% confidence interval 2.30-10.86). Median survival for HIV-positive patients from the start of treatment was 22 months. At least 34% of HIV-positive patients for whom cause of death was known died from tuberculosis, three-quarters of these during the first month of treatment. Risk factors for death in HIV-positive patients included multi-site tuberculosis, history of prolonged diarrhoea or fever, oral thrush, splenomegaly, anergy to tuberculin, low weight, anaemia or lymphopenia, and poor compliance with regimens containing rifampicin and pyrazinamide. Tuberculosis, even treated, was a major cause of death in patients with HIV infection.

PIP: The impact of HIV on mortality is described in a prospective study of tuberculosis patients in Lusaka, Zambia, where more than 70% of newly diagnosed tuberculosis patients have concurrent HIV infection. Patients attending the University Teaching Hospital in Lusaka, Zambia, were recruited to a prospective cohort study from April to December 1989. Of the 239 patients included in the follow-up study, 174 (73%) were HIV-1 positive by ELISA. A higher proportion of HIV-positive patients were 25-34 years old, and they more often had a negative tuberculin response, anemia, or lymphopenia at recruitment. The probability of survival for HIV-negative and HIV-positive patients was, respectively: at 2 months 95% and 89%; at 6 months 95% and 76%; at 12 months 91% and 66%; at 18 months 87% and 55%; and at 24 months 87% and 48%. The median survival of HIV-positive patients was 22 months. The crude, 2-year mortality rate ratio for HIV-positive compared with HIV-negative patients was 5 (p 0.001). Mortality was higher for patients with both pulmonary and extrapulmonary disease than for those with either pulmonary or extrapulmonary disease alone; for individual sites, only lymph node disease was associated with a significantly higher mortality than other sites (p = 0.01). At presentation prolonged fever, prolonged diarrhea, oral Candida or splenomegaly, negative tuberculin response, anemia or lymphopenia and low weight were associated with higher mortality. Among the 39 patients seen at 2 months who had been prescribed short-course chemotherapy, subsequent mortality was lower in the group who reported receiving all 60 doses of either rifampicin or pyrazinamide or both (20 patients) than among those who had not (19 patients¿ (rate ratio 0.24, p = 0.02). 47 of the 81 patients died within 24 months of the start of treatment, 5 HIV-negative and 42 HIV-positive. 3 of 5 HIV-negative patients for whom information was available died of active tuberculosis. Among HIV-positive patients, 14 of 42 died of active tuberculosis and 2 more of complications of tuberculosis.

Bed occupancy due to HIV/AIDS in an urban hospital medical ward in Uganda.

OBJECTIVE: To determine the proportion of patients with HIV-related illness admitted to a medical ward. DESIGN: A prospective study. SETTING: Rubaga Hospital, the third largest hospital in Kampala, the capital of Uganda. PARTICIPANTS: A total of 449 patients admitted to the medical ward between September and November 1992. RESULTS: Of the 449 patients, 390 (86.8%) agreed to provide a blood sample for HIV serology. Of these, 55.6% (95% confidence interval, 50.7-60.5%) were positive for HIV. Eighty-six (22.2%) of all patients [71 (33%) of the seropositives and six (3.5%) of the seronegatives] met the World Health Organization case definition for AIDS in Africa. The HIV-seropositives had a mortality rate of 17.4%, significantly higher (P = 0.00057) than the 5.8% rate observed in the seronegative group. The overall mortality rate was 13.7% and was significantly associated with HIV infection (P = 0.0005). CONCLUSION: HIV infection is a major contributor to morbidity and mortality in Uganda. Over 50% of the medical admissions were HIV-positive revealing the serious impact of HIV on the health-care system.

The impact of HIV on infectiousness of pulmonary tuberculosis: a community study in Zambia.

OBJECTIVE: To examine the impact of HIV on infectiousness of pulmonary tuberculosis (TB). DESIGN: A cross-sectional tuberculin survey carried out among household contacts of HIV-1-positive and negative patients with bacteriologically confirmed pulmonary TB. Contacts were also examined for active TB. SETTING: Index cases were recruited from patients attending the University Teaching Hospital in Lusaka, Zambia and household contacts were examined during visits to their homes within Lusaka. PATIENTS, PARTICIPANTS: A total of 207 contacts of 43 HIV-positive patients, and 141 contacts of 28 HIV-negative patients with pulmonary TB were examined. MAIN OUTCOME MEASURES: Proportion of contacts of HIV-positive and negative index cases with a positive tuberculin response (diameter of induration > or = 5 mm to a dose of 2 tuberculin units). RESULTS: Fifty-two per cent of contacts of HIV-positive pulmonary TB patients had a positive tuberculin response compared with 71% of contacts of HIV-negative patients (odds ratio, 0.43; 95% CI, 0.26-0.72; P < 0.001). This difference persisted after allowing for between-household variations in the tuberculin response. Tuberculin response in the contact was related to age of contact, intimacy with the index case and crowding in the household. However, the effect of HIV status of the index case was not confounded by these variables. Tuberculin response in the contact was also related to the number of bacilli seen in the sputum smear of the index case which partially explained the effect of HIV status of the index case. Active TB was diagnosed in 4% of contacts of HIV-positive and 3% of contacts of HIV-negative cases, respectively (P = 0.8). CONCLUSIONS: HIV-positive patients with pulmonary TB may be less infectious than their HIV-negative counterparts and this may partly be explained by lower bacillary load in the sputum.

PIP: Between April and December 1989, the chest clinic of the University Teaching Hospital in Lusaka, Zambia, confirmed pulmonary tuberculosis (TB) in 141 adults, 95 (67%) of whom were HIV-1 seropositive. Health workers made home visits to 71 of the index cases (43 HIV-1 positive and 28 HIV-1 negative) to learn whether the 348 household members would also develop TB, thus allowing researchers to determine the effect of HIV on infectiousness of TB. Contacts of HIV-1 positive patients developed TB at a lower rate than did those of HIV-1 negative patients (52% vs. 71%; odds ratio [OR] = 0.43; p .001). This difference continued even after controlling for between-household variations, indicating that confounding variables did not account for the difference. Age of contact, intimacy with the index case, and crowding in the household were associated with the tuberculin response in the contact, but they did not confound the effect of HIV status. Tuberculin response in the contact was associated with the number of bacilli in the sputum smear (crude OR = 3.13; p = .013, and adjusted OR =1.84; p = .28), suggesting that the number of bacilli somewhat explained the difference in infectiousness between HIV-1 positive and HIV-1 negative patients. 12 contacts (8 of HIV-positive cases and 4 of HIV-negative cases) developed active TB after the TB diagnosis in the index case. These findings clearly demonstrated that infection with Mycobacterium tuberculosis was less likely in household members of HIV-1 positive cases than in those of HIV-1 negative cases. The lower bacillary load in the sputum in HIV- 1 cases may have accounted somewhat for the lower infectiousness of pulmonary TB.

The impact of human immunodeficiency virus on presentation and diagnosis of tuberculosis in a cohort study in Zambia.

Two hundred and forty-nine patients with tuberculosis were recruited to a cohort study to investigate the interaction between tuberculosis and HIV in Lusaka, Zambia; findings at presentation are presented here. One hundred and eighty-two (73%; 95% confidence interval 67-79%) of the cases were HIV-1 antibody positive. The diagnosis of tuberculosis was confirmed by microscopy for acid-alcohol fast bacilli, culture of Mycobacterium tuberculosis, or histology in 74% of all cases. HIV negative and positive cases differed in site of disease: among HIV negative patients 72% had pulmonary disease alone, 16% extrapulmonary disease alone and 12% had both, whereas among HIV positive patients 40% had pulmonary disease alone, 34% extrapulmonary disease alone and 26% both (P < 0.001). HIV negative and positive cases were compared with regard to outcome of diagnostic procedures: 55% of HIV negative cases could be diagnosed at enrollment by sputum smear, but only 35% of HIV positive cases (P < 0.01). Among pulmonary cases confirmed by sputum culture, 76% of HIV negative patients had a positive sputum smear, compared with 57% of HIV positive patients (P = 0.09). Pleural and pericardial disease were difficult to confirm, but culture of pleural fluid was positive in 12/46 HIV positive patients, compared with 0/11 HIV negative patients. Lymph node disease was readily confirmed by biopsy. The tuberculin test was positive in only 30/110 (27%) of HIV positive cases, but in 21/38 (55%) of HIV negative cases (P < 0.01). Mycobacterium tuberculosis was cultured in 57% of HIV negative cases and 54% of HIV positive cases; no atypical mycobacteria were isolated. Initial resistance to isoniazid was present in isolates from 5% of cases with a positive culture.

Impact of HIV on tuberculosis in Zambia: a cross sectional study.

OBJECTIVE: To examine the contribution of HIV infection to the apparently increasing incidence of tuberculosis in central Africa. DESIGN: Cross sectional study. SETTING: Outpatient clinic in teaching hospital, Lusaka, Zambia. PATIENTS: 346 Adult patients with tuberculosis. RESULTS: Overall, 206 patients (60%; 95% confidence interval 54% to 65%) were positive for HIV: in one or both assays used. The peaks for both tuberculosis and HIV infection were among men aged 25-34 years and women aged 14-24 years. Of patients with confirmed pulmonary tuberculosis, 73/149 (49%; 41% to 57%) were positive for HIV; 67/83 (81%; 70% to 89%) patients with pleural disease and 16/19 (84%; 60% to 97%) patients with pericardial disease were positive. HIV positive patients with positive sputum culture were less likely to have had a positive sputum smear, and their chest x ray films less often showed classic upper zone disease or cavitation. Of 72 patients who fulfilled clinical criteria for AIDS, 17 were negative for HIV. CONCLUSIONS: The high prevalence of HIV in patients with tuberculosis suggests that an epidemic of reactivating tuberculosis is arising in those who are infected with HIV. The redirection of public health priorities towards tuberculosis would focus on a major treatable and preventable complication of the AIDS epidemic.

PIP: To examine the contribution of HIV infection to the apparently increasing incidence of tuberculosis patients of an outpatient clinic in a teaching hospital in Lusaka, Zambia. Overall, 206 patients (60%) tested positive for HIV. The peaks for both tuberculosis and HIV infection were among men aged 25-34 years and women aged 14-24 years. Of patients with confirmed pulmonary tuberculosis, 49% were positive for HIV. 81% of patients with pleural disease and 84% of patients with pericardial disease were positive. HIV positive patients with a positive sputum culture were less likely to have had a positive sputum smear, and their chest x-ray films less often showed classic upper zone disease or cavitation. Of 72 patients who fulfilled clinical criteria for AIDS, 17 were negative for HIV. In conclusion, the high prevalence of HIV in patients with tuberculosis suggests that an epidemic of reactivating tuberculosis is arising in those who are infected with HIV. The redirection of public health priorities towards tuberculosis would focus on a major treatable and preventable complication of the AIDS epidemic.

Apparent vertical transmission of human immunodeficiency virus type 1 by breast-feeding in Zambia.

PIP: To evaluate the epidemiologic significance of breastfeeding to the transmission of human immunodeficiency virus (HIV) in a country with a high prevalence of HIV infection, the 1720 seronegative women who delivered at the University Teaching Hospital in Lusaka, Zambia, in a 3- month period in 1987 were enrolled in a longitudinal study. Only 634 (37%) of these women returned for testing at the 1-year follow-up point. Of these, 19 (3%) had become seropositive. The infection was asymptomatic in all 19 women at the time of the 1-year follow-up; however, 5 of these women soon developed generalized persistent adenopathy and 3 had spontaneous abortions during the year in which seroconversion occurred. 30 of the spouses of the women in the study sample were HIV-positive; the relative risk of seroconversion was 3.84 in women with HIV-infected spouses compared to those with HIV-negative spouses. Other significant risk factors for HIV seroconversion included: history of genital ulceration after delivery (relative risk, 15.51), use of a cloth to remove vaginal secretions during intercourse (dry sex) (relative risk, 37.95), and blood transfusion (relative risk, 10.89). 3 infants born to these 19 women also seroconverted; 2 years after seroconversion, only 1 of the 3 infected children was symptomatic (persistent, generalized lymphadenopathy). Other sources of HIV infection 9e.g., scarification, blood transfusions, use of contaminated needles during immunization) aside from breastfeeding were not recorded in these 3 infants. Although there is a high prevalence of HIV infection in Zambia, the health benefits of breastfeeding (in terms of the prevention of mortality from diarrheal disease) still outweigh the small risk of HIV transmission.^ieng

Syphilis intervention in pregnancy: Zambian demonstration project.

Despite availability of simpler serologic tests for syphilis and near cure with penicillin, unacceptably high prevalence of infectious maternal syphilis exist in many developing countries, including Zambia. It is the foremost risk factor for mid-trimester abortions, stillbirths, prematurity and morbidity and mortality among infants born with congenital syphilis in Zambia. An intervention project was conducted in Lusaka aimed at demonstrating the effectiveness of new health education methods and prenatal screening for syphilis in reducing the adverse outcomes during pregnancy. During pre-intervention phase, approximately 150 consecutive pregnant women from each of the three study and the three control centres were recruited when they presented in labour at the University Teaching Hospital. The intervention phase lasted for one year at the three study centres during which new methods of health education were introduced to improve early attendances during pregnancy. Also, on-site syphilis screening was performed twice during pregnancy and seroreactive women, and in many cases their sexual partners, were treated by the existing prenatal clinic staff. During the post-intervention phase the steps of pre-intervention phase were repeated to evaluate the impact of intervention. Overall, 8.0% of women were confirmed seroreactive for syphilis; there was no difference between the study and the control centres (p greater than 0.05). Fifty seven percent (132/230) of syphilitic pregnancies ended with an adverse outcome, that is, abortion (RR 5.0), stillbirth (RR 3.6), prematurity (RR 2.6) and low birth weight (RR 7.8). The overall risk of adverse outcomes due to syphilis was 8.29 (95% confidence interval 6.53, 10.53). The new methods of health education were effective and the percentage of women who had their first prenatal visit under 16 weeks of gestation improved from 9.4 to 42.5. Although screening and treatment during intervention was suboptimal, the adverse outcomes attributable to syphilis were reduced to 28.3%; this is almost a two-third reduction when compared with 72.4% of adverse outcomes at control centres (p < less than 0.001). The intervention is culturally and politically acceptable in Zambia. The cost of each prenatal screening is US$0.60 and of averting each adverse outcome US$12. In countries with high rates of syphilis, there is an urgent need for STD control and Maternal and Child Health (MCH) programmes to pool their resources together to revitalise the prenatal care.

PIP: Researchers at the University Teaching Hospital in Lusaka, Zambia implemented their syphilis intervention project in 3 phases: preintervention phase (September 1985-January 1986), intervention phase (February 1986-January 1987), and postintervention phase (February-June 1987). To evaluated the effectiveness of the project, they followed 491 women from 3 periurban health centers serving as study centers and 434 from 3 similar control centers. 8% of all women tested positive for syphilis which was lower than seroprevalence for prenatal patients in 1980 and 1983 (12.5% and 12.8% respectively). Before intervention, 9.4% of the women visited a health center for the 1st prenatal visit before 16 weeks gestation. Following health education during the intervention phase, this percentage climbed to 42.5%. Health workers conducted a syphilis test on 58.6% and 14.3% of the women during their 1st visit to a study center and control center respectively. Prior to intervention, adverse outcomes occurred in 58% of syphilitic pregnancies. Total relative risk (RR) for adverse outcomes stood at 8.29. Specifically, RR was 7.76 for low birth weight, 5.03 for abortion, 3.57 for stillbirth, and 2.61 for premature birth. 2.2% of the syphilitic pregnancies resulted in congenital syphilis. Before penicillin was available for treatment these percentages were 20-40% abortions, 20-30% stillbirths, and 25% congenital infections. After the intervention phase, syphilitic pregnancies resulted in 28.3% adverse outcomes (p.001). The percentage of adverse outcomes at the control centers stood at 72.4%. Further, nonsyphilitic pregnancies resulted in 11.1% adverse outcomes before intervention and 8.1% following intervention (p.05). This study showed that syphilis intervention is effective and not costly (US$12 to prevent each adverse outcome).

Perinatal transmission of HIV-I in Zambia.

OBJECTIVE--To determine the occurrence of vertical transmission of HIV-I from women positive for the virus and the prognosis for their babies. DESIGN--Women presenting in labour were tested for HIV-I. Their newborn babies were also tested. Women positive for the virus were followed up with their babies for two years. SETTING--Teaching hospital in Lusaka, Zambia. SUBJECTS--1954 Women, of whom 227 were seropositive. Of 205 babies, 192 were positive for HIV-I. After birth 109 seropositive mothers and their babies and 40 seronegative mothers and their babies were available for follow up. MAIN OUTCOME MEASURES--Serological examination of mothers and their babies by western blotting. Birth weight and subsequent survival of babies. Women and babies were tested over two years for signs of seroconversion and symptoms of infection with HIV, AIDS related complex, and AIDS. RESULTS--Of the 109 babies born to seropositive mothers and available for follow up, 18 died before 8 months, 14 with clinical AIDS. Of the 91 remaining, 23 were seropositive at 8 months. By 24 months 23 of 86 surviving babies were seropositive, and a further five infected babies had died, four were terminally ill, 17 had AIDS related complex, and two had no symptoms. The overall rate of perinatal transmission was 42 out of 109 (39%). The overall mortality of infected children at 2 years was 19 out of 42 (44%). Before the age of 1 year infected children had pneumonia and recurrent coughs, thereafter symptoms included failure to thrive, recurrent diarrhoea and fever, pneumonia, candidiasis, and lymphodenopathy. All babies had received live attenuated vaccines before 8 months with no adverse affects. CONCLUSIONS--Vertical transmission from infected mothers to their babies is high in Zambia and prognosis is poor for the babies. Perinatal transmission and paediatric AIDS must be reduced, possibly by screening young women and counselling those positive for HIV-I against future pregnancy.