Adverse maternal outcomes and associated factors among mothers of advanced age delivering at a tertiary hospital, southwestern Uganda: a cross-sectional study.

BACKGROUND: Mothers of advanced age, defined as pregnant women aged ≥ 35 years at the time of giving birth, are traditionally known to be associated with increased risks of adverse maternal outcomes. We determined the prevalence of adverse maternal outcomes and associated factors among mothers of advanced age who delivered at Kabale Regional Referral Hospital (KRRH), in Southwestern Uganda. METHODS: We conducted a cross-sectional study at the Maternity Ward of KRRH from April to September 2023. We consecutively enrolled pregnant women aged ≥ 35 years during their immediate post-delivery period and before discharge. We obtained data on their socio-demographic, obstetric, medical characteristics and their maternal outcomes using interviewer-administered questionnaires. We defined adverse maternal outcome as any complication sustained by the mother that was related to pregnancy, delivery and immediate post-partum events (obstructed labour, antepartum haemorrhage, mode of delivery [cesarean or vacuum extraction], postpartum haemorrhage, hypertensive disorders of pregnancy, preterm or postdate pregnancy, anemia, premature rupture of membranes, multiple pregnancy, and maternal death). A participant was considered to have an adverse outcome if they experienced any one of these complications. We identified factors associated with adverse outcomes using modified Poisson regression. RESULTS: Out of 417 participants, most were aged 35-37 years (n = 206; 49.4%), and had parity ≥ 5 (65.5%). The prevalence of adverse maternal outcomes was 37.6% (n = 157, 95%CI: 33.1-42.4%). Common adverse maternal outcomes included caesarian delivery (23%), and obstructed labour (14.4%). Other complications included anemia in pregnancy (4.5%), chorioamnionitis (4.1%), preterm prelabour rupture of membranes (3.9%), and chronic hypertension and preeclampsia (both 2.4%). Factors associated with adverse maternal outcomes were precipitate labour (adjusted prevalence ratio [aPR] = 1.95, 95%CI: 1.44-2.65), prolonged labour, lasting > 12 h (aPR = 2.86, 95%CI: 1.48-3.16), and chronic hypertension (aPR = 2.01, 95%CI: 1.34-3.9). CONCLUSION: Approximately two-fifth of the advanced-aged mothers surveyed had adverse outcomes. Mothers with prolonged labour, precipitate labour and chronic hypertension were more likely to experience adverse outcomes. We recommend implementation of targeted interventions, emphasizing proper management of labor as well as close monitoring of hypertensive mothers, and those with precipitate or prolonged labor, to mitigate risks of adverse outcomes within this study population.

Uganda's experience in establishing an electronic compendium for public health emergencies.

Uganda has implemented several interventions that have contributed to prevention, early detection, and effective response to Public Health Emergencies (PHEs). However, there are gaps in collecting and documenting data on the overall response to these PHEs. We set out to establish a comprehensive electronic database of PHEs that occurred in Uganda since 2000. We constituted a core development team, developed a data dictionary, and worked with Health Information Systems Program (HISP)-Uganda to develop and customize a compendium of PHEs using the electronic Integrated Disease Surveillance and Response (eIDSR) module on the District Health Information Software version 2 (DHIS2) platform. We reviewed literature for retrospective data on PHEs for the compendium. Working with the Uganda Public Health Emergency Operations Center (PHEOC), we prospectively updated the compendium with real-time data on reported PHEs. We developed a user's guide to support future data entry teams. An operational compendium was developed within the eIDSR module of the DHIS2 platform. The variables for PHEs data collection include those that identify the type, location, nature and time to response of each PHE. The compendium has been updated with retrospective PHE data and real-time prospective data collection is ongoing. Data within this compendium is being used to generate information that can guide future outbreak response and management. The compendium development highlights the importance of documenting outbreak detection and response data in a central location for future reference. This data provides an opportunity to evaluate and inform improvements in PHEs response.

Women's recommendations: vacuum extraction or caesarean section for prolonged second stage of labour, a prospective cohort study in Uganda.

OBJECTIVES: To investigate what women who have experienced vacuum extraction or second stage caesarean section (CS) would recommend as mode of birth in case of prolonged second stage of labour. METHODS: A prospective cohort study was conducted in a tertiary referral hospital in Uganda. Between November 2014 and July 2015, women with a term singleton in vertex presentation who had undergone vacuum extraction or second stage CS were included. The first day and 6 months after birth women were asked what they would recommend to a friend: vacuum extraction or CS and why. Outcome measures were: proportions of women choosing vacuum extraction vs. CS and reasons for choosing this mode of birth. RESULTS: The first day after birth, 293/318 (92.1%) women who had undergone vacuum extraction and 176/409 (43.0%) women who had undergone CS recommended vacuum extraction. Of women who had given birth by CS in a previous pregnancy and had vacuum extraction this time, 31/32 (96.9%) recommended vacuum extraction. Six months after birth findings were comparable. Less pain, shorter recovery period, avoiding surgery and the presumed relative safety of vacuum extraction to the mother were the main reasons for preferring vacuum extraction. Main reasons to opt for CS were having experienced CS without problems, CS presumed as being safer for the neonate, CS being the only option the woman was aware of, as well as the concern that vacuum extraction would fail. CONCLUSIONS: Most women would recommend vacuum extraction over CS in case of prolonged second stage of labour.

OBJECTIFS: Investiguer ce que les femmes qui ont subi une extraction sous vide ou une césarienne au second stade du travail recommanderaient comme mode d'accouchement en cas de second stade prolongé du travail. MÉTHODES: Une étude de cohorte prospective a été menée dans un hôpital de référence tertiaire en Ouganda. Entre novembre 2014 et juillet 2015, les femmes avec un singleton à terme en présentation de vertex ayant subi une extraction sous vide ou une césarienne de second stade ont été incluses. Le premier jour et six mois après la naissance, on a demandé aux femmes ce qu'elles recommanderaient à une amie: l'extraction sous vide ou la césarienne et pourquoi. Les résultats mesurés étaient: les proportions de femmes choisissant l'extraction sous vide par rapport à la césarienne et les raisons de choisir ce mode d'accouchement. RÉSULTATS: Le premier jour après l'accouchement, 293/318 femmes (92,1%) ayant subi une extraction sous vide et 176/409 (43,0%) femmes ayant subi une césarienne ont recommandé l'extraction sous vide. Parmi les femmes qui avaient accouché par césarienne dans une grossesse précédente et qui avaient eu une extraction sous vide cette fois-ci, 31/32 (96,9%) ont recommandé l'extraction sous vide. Six mois après la naissance, les résultats étaient comparables. Moins de douleur, une période de convalescence plus courte, l'évitement de la chirurgie et la sécurité relative présumée de l'extraction sous vide pour la mère étaient les principales raisons de préférer l'extraction sous vide. Les principales raisons d'opter pour la césarienne étaient l'expérience d'avoir subi une césarienne sans problèmes, la césarienne étant supposée être plus sûre pour le nouveau-né, la césarienne étant la seule option dont la femme était au courant, ainsi que la crainte d'un éventuel échec de l'extraction sous vide. CONCLUSIONS: La plupart des femmes recommanderaient l'extraction sous vide plutôt que la césarienne en cas de second stade prolongé du travail.

Birthing experience and quality of life after vacuum delivery and second-stage caesarean section: a prospective cohort study in Uganda.

OBJECTIVE: To assess perceptions of women undergoing vacuum extraction or second-stage caesarean section (SSCS) in a tertiary referral hospital in sub-Saharan Africa. METHODS: Prospective cohort study, with six-month follow-up, of women who gave birth to a term singleton in cephalic presentation by vacuum extraction (n = 289) or SSCS (n = 357) between 25 November 2014, to 8 July 2015, in Mulago Hospital, Uganda. Excluded were women who had failed vacuum extraction, severe birth complications and those whose babies had died. Outcome measures were birthing experience satisfaction, physical component summary (PCS) and mental component summary (MCS) of the SF-12 quality-of-life questionnaire, pain scores and dyspareunia. RESULTS: One day after vacuum extraction, 63.7% (181/284) of women were feeling well vs. 48.1% (167/347) after SSCS (OR 1.89; 95%CI 1.37-2.61) and mean pain sores were 2.70 vs. 3.87 (P < 0.001). In both groups, >90% of women were satisfied with their birthing experience. At six weeks, in vacuum extraction vs. SSCS, mean pain sores were 0.40 vs. 0.89 (P < 0.001); mean PCS was 48.67 vs. 44.03 (P < 0.001); mean MCS was 52.80 vs. 51.23 (P = 0.203); 40% (70/175) vs. 28.3% (70/247) of women had resumed sexual intercourse (OR 1.69; 95%CI 1.12-2.54) and 21.4% (15/70) vs. 28.6% (20/70) had dyspareunia (OR 0.68; 95%CI 0.32-1.47). No differences were found at six months after birth. CONCLUSION: One day and six weeks after birth, outcomes were better in women who had vacuum extraction. At six months, outcomes were similar. To promote quick recovery, vacuum extraction should be the first intervention considered in the second stage of labour.

Prospective cohort study comparing outcomes between vacuum extraction and second-stage cesarean delivery at a Ugandan tertiary referral hospital.

OBJECTIVE: To compare maternal and perinatal outcomes between vacuum extraction and second-stage cesarean delivery (SSCD). METHODS: The present observational cohort study was conducted among women with term vertex singleton pregnancies who underwent vacuum extraction or SSCD at Mulago National Referral Hospital, Kampala, Uganda, between November 25, 2014, and July 8, 2015. Severe maternal outcomes (mortality, uterine rupture, hysterectomy, re-laparotomy) and perinatal outcomes (mortality, trauma, low Apgar score, convulsions) were compared between initial delivery mode. RESULTS: Among 13 152 deliveries, 358 women who underwent vacuum extraction and 425 women who underwent SSCD were enrolled in the study. No maternal deaths occurred after vacuum extraction versus five deaths from complications of SSCD. Vacuum extraction was associated with less severe maternal outcomes compared with SSCD (3 [0.8%] vs 18 [4.2%]; adjusted odds ratio [aOR] 0.24, 95% confidence interval [CI] 0.07-0.84). Fetal death during the decision-to-delivery interval was also less common in the vacuum extraction group (3 [0.9%] vs 18 [4.4%]; aOR 0.24, 95% CI 0.07-0.84); however, the perinatal mortality rate did not differ between the vacuum extraction and SSCD groups (29 [8.4%] vs 45 [11.0%], respectively; aOR 0.83, 95% CI 0.49-1.41). One infant in each group exhibited neurodevelopmental anomalies at 6 months. CONCLUSION: Vacuum extraction had better maternal outcomes and equivalent perinatal outcomes compared with SSCD. These findings encourage re-introduction of vacuum extraction.

Audit of a program to increase the use of vacuum extraction in Mulago Hospital, Uganda.

BACKGROUND: Prolonged second stage of labour is a major cause of perinatal and maternal morbidity and mortality in low-income countries. Vacuum extraction is a proven effective intervention, hardly used in Africa. Many authors and organisations recommend (re)introduction of vacuum extraction, but successful implementation has not been reported. In 2012, a program to increase the use of vacuum extraction was implemented in Mulago Hospital, Uganda. The program consisted of development of a vacuum extraction guideline, supply of equipment and training of staff. The objective of this study was to investigate the impact of the program. METHODS: Audit of a quality improvement intervention with before and after measurement of outcome parameters. SETTING: Mulago Hospital, the national referral hospital for Uganda with approximately 33 000 deliveries per year. It is the university teaching hospital for Makerere University and most of the countries doctors and midwives are trained here. Data was collected from hospital registers and medical files for a period of two years. Main outcome measures were vacuum extraction rate, intrapartum stillbirth, neonatal death, uterine rupture, maternal death and decision to delivery interval. RESULTS: Mode of delivery and outcome of 12 143 deliveries before and 34 894 deliveries after implementation of the program were analysed. The vacuum extraction rate increased from 0.6 - 2.4 % of deliveries (p < 0.01) and was still rising after 18 months. There was a decline in intrapartum stillbirths from 34 to 26 per 1000 births (-23.6 %, p < 0.01) and women with uterine rupture from 1.1 - 0.8 per 100 births (-25.5 %, p < 0.01). Decision to delivery interval for vacuum extraction was four hours shorter than for caesarean section. CONCLUSIONS: A program to increase the use of vacuum extraction was successful in a high-volume university hospital in sub-Saharan Africa. The use of vacuum extraction increased. An association with improved maternal and perinatal outcome is strongly suggested. We recommend broad implementation of vacuum extraction, whereby university hospitals like Mulago Hospital can play an important role.To support implementation, we recommend further research into outcome of vacuum extraction and into vacuum extraction devices for low-income countries. Such studies are now in progress at Mulago Hospital.

Screening for abnormal vaginal microflora by self-assessed vaginal pH does not enable detection of sexually transmitted infections in Ugandan women.

OBJECTIVE: Is self-assessed vaginal pH measurement to detect abnormal vaginal bacterial microflora (AVF) an adequate prescreening method for detection of genital sexually transmitted infections (STIs)? MATERIALS AND METHODS: A total of 360 Ugandan women tested themselves with a gloved finger and a pH color strip. PCR for bacterial vaginosis (BV)-associated bacteria was tested by PCR for Mycoplasma hominis, Ureaplasma urealyticum, and/or Atopobium vaginae, while the STIs were diagnosed by positive PCR for Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, and/or Trichomonas vaginalis. RESULTS: A strong correlation was found between self-assessed pH values and BV-associated bacteria (P<0.0001), but not with STIs, not as single infections, nor in general. CONCLUSION: Self-measured vaginal pH correlated well with markers of high-risk microflora types such as BV or aerobic vaginitis, but not with STIs. Hence, in a screening program addressing AVF in low-resource countries, extra specific tests are required to exclude STIs.

Shifts in geographic distribution and antimicrobial resistance during a prolonged typhoid fever outbreak--Bundibugyo and Kasese Districts, Uganda, 2009-2011.

BACKGROUND: Salmonella enterica serovar Typhi is transmitted by fecally contaminated food and water and causes approximately 22 million typhoid fever infections worldwide each year. Most cases occur in developing countries, where approximately 4% of patients develop intestinal perforation (IP). In Kasese District, Uganda, a typhoid fever outbreak notable for a high IP rate began in 2008. We report that this outbreak continued through 2011, when it spread to the neighboring district of Bundibugyo. METHODOLOGY/PRINCIPAL FINDINGS: A suspected typhoid fever case was defined as IP or symptoms of fever, abdominal pain, and ≥1 of the following: gastrointestinal disruptions, body weakness, joint pain, headache, clinically suspected IP, or non-responsiveness to antimalarial medications. Cases were identified retrospectively via medical record reviews and prospectively through laboratory-enhanced case finding. Among Kasese residents, 709 cases were identified from August 1, 2009-December 31, 2011; of these, 149 were identified during the prospective period beginning November 1, 2011. Among Bundibugyo residents, 333 cases were identified from January 1-December 31, 2011, including 128 cases identified during the prospective period beginning October 28, 2011. IP was reported for 507 (82%) and 59 (20%) of Kasese and Bundibugyo cases, respectively. Blood and stool cultures performed for 154 patients during the prospective period yielded isolates from 24 (16%) patients. Three pulsed-field gel electrophoresis pattern combinations, including one observed in a Kasese isolate in 2009, were shared among Kasese and Bundibugyo isolates. Antimicrobial susceptibility was assessed for 18 isolates; among these 15 (83%) were multidrug-resistant (MDR), compared to 5% of 2009 isolates. CONCLUSIONS/SIGNIFICANCE: Molecular and epidemiological evidence suggest that during a prolonged outbreak, typhoid spread from Kasese to Bundibugyo. MDR strains became prevalent. Lasting interventions, such as typhoid vaccination and improvements in drinking water infrastructure, should be considered to minimize the risk of prolonged outbreaks in the future.

The impact of highly active antiretroviral therapy on high-risk behaviour of HIV-infected patients in sub-Saharan Africa.

INTRODUCTION: High-risk sexual behaviors such as multiple sexual partners, inconsistent condom use, acquisition of sexually transmitted infection (STIs), and non-use of contraceptives persist in HIV patients undergoing care. We conducted a systematic review of studies conducted in the era of increased access to HAART (2000-2010) to assess whether wide-scale use of HAART was associated with high-risk behavior among HAART-using patients. METHODOLOGY: We conducted a comprehensive search of databases (AIDSLINE, National Library of Medicine, MEDLINE, PubMed, CINHAL and EMBASE) from January 2002 to January 2010, reviewed conference proceedings and journals, and contacted the researchers involved. We analyzed the association of high-risk behaviors (non-disclosure of sero-status to sexual partners, inconsistent condom use, unprotected sexual intercourse, multiple sexual partners, non-use of contraceptives and acquisition of STIs) with using HAART. Information from eligible studies was abstracted using a standardized checklist. Fourteen English-language studies met the selection criteria of having high-risk behavior as an outcome in patients using HAART in sub-Saharan Africa. RESULTS: Of the 92 eligible articles screened, 14 met the criteria for inclusion as primary articles, 10 showed that HAART is not associated with increased high-risk behavior, two showed increase in acquisition of STIs among HAART-using patients, (which was inconsistent with other measures of high-risk behavior), and two studies showed short-term increase in high-risk behavior. CONCLUSIONS: Persistence of high-risk behavior in HAART-using patients suggests that more effort needs to be incorporated in HIV care to reduce such behavior to reduce HIV transmission to uninfected populations.

Plasmodium falciparum dihydrofolate reductase and dihyropteroate synthase mutations and the use of trimethoprim-sulfamethoxazole prophylaxis among persons infected with human immunodeficiency virus.

A prospective cohort design was used to measure the association between daily cotrimoxazole-prophylaxis and infection with Plasmodium falciparum containing mutations associated with antifolate resistance among persons infected with human immunodeficiency virus (HIV) in Tororo and Busia District, in eastern Uganda. Of 149 cases of P. falciparum parasitemia diagnosed, 147 (99%) (smears from participants taking prophylaxis = 91 and smears from those not taking cotrimoxazole prophylaxis = 56) were successfully assessed for mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutations associated with antifolate resistance. Prevalences of the dhfr pure triple mutant (74% and 70%; P = 0.71), the dhps pure double mutant (95% and 88%; P = 0.21), and the dhfr/dhps pure quintuple mutant (73% and 64%; P = 0.36), were not significantly different between those taking and those not taking cotrimoxazole-prophylaxis, respectively. The overall prevalence of the pure quintuple mutant in this study was 69%, which is among the highest in Africa. Although resistance rates of P. falciparum to antifolate drugs are high, cotrimoxazole-prophylaxis in HIV-infected persons was not associated with a higher prevalence of mutations associated with antifolate resistance.

Outcome of cesarean section in asymptomatic HIV-1 infection in Kampala, Uganda.

AIM: Sepsis remains a major cause of morbidity and mortality in Mulago Hospital, Kampala, Uganda, following cesarean section (CS). The present study was designed to assess whether asymptomatic HIV infection could be contributing to the increased morbidity following emergency CS in the form of wound and genital tract infection (GTI) with consequent prolonged stay in the hospital. METHODS: Five hundred patients who had undergone emergency lower segment CS had their blood taken to check for HIV-1 serostatus on the first postoperative day. The patients were followed up for evidence of wound sepsis, defined as occult pus discharge on compression of the wound or removal of the closing stitches, GTI and duration of stay in the hospital after the operation. RESULTS: There were 98 (20.5%) HIV-1 seropositive patients. The incidence of postoperative wound sepsis (P = 0.948, 95% confidence interval [CI] 0.56-1.86), GTI (P = 0.339, 95% CI = 0.74-2.39) as well as hospital stay >8 days (P = 0.327, 0.78-2.09) was not statistically significantly different between the infected and non-infected groups. Significant predisposing factors to postoperative morbidity were poor general condition on admission, dehydration, preoperative clinical anemia, and ruptured membranes prior to the operation. CONCLUSION: Asymptomatic HIV-1 was not associated with increased postoperative morbidity following emergency lower segment cesarean section.

Mortality in HIV-infected Ugandan adults receiving antiretroviral treatment and survival of their HIV-uninfected children: a prospective cohort study.

BACKGROUND: Antiretroviral therapy (ART) is increasingly available in Africa, but physicians and clinical services are few. We therefore assessed the effect of a home-based ART programme in Uganda on mortality, hospital admissions, and orphanhood in people with HIV-1 and their household members. METHODS: In 2001, we enrolled and followed up 466 HIV-infected adults and 1481 HIV-uninfected household members in a prospective cohort study. After 5 months, we provided daily co-trimoxazole (160 mg trimethoprim and 800 mg sulfamethoxazole) prophylaxis to HIV-infected participants. Between May, 2003, and December, 2005, we followed up 138 infected adults who were eligible and 907 new HIV-infected participants and their HIV-negative household members in a study of ART (mainly stavudine, lamivudine, and nevirapine). Households were visited every week by lay providers, and no clinic visits were scheduled after enrolment. We compared rates of death, hospitalisation, and orphanhood during different study periods and calculated the number needed to treat to prevent an outcome. FINDINGS: 233 (17%) of 1373 participants with HIV and 40 (1%) of 4601 HIV-uninfected household members died. During the first 16 weeks of ART and co-trimoxazole, mortality in HIV-infected participants was 55% lower than that during co-trimoxazole alone (14 vs 16 deaths per 100 person-years; adjusted hazard ratio 0.45, 95% CI 0.27-0.74, p=0.0018), and after 16 weeks, was reduced by 92% (3 vs 16 deaths per 100 person-years; 0.08, 0.06-0.13, p<0.0001). Compared with no intervention, ART and co-trimoxazole were associated with a 95% reduction in mortality in HIV-infected participants (5 vs 27 deaths per 100 person-years; 0.05, 0.03-0.08, p<0.0001), 81% reduction in mortality in their uninfected children younger than 10 years (0.2 vs 1.2 deaths per 100 person-years; 0.19, 0.06-0.59, p=0.004), and a 93% estimated reduction in orphanhood (0.9 vs 12.8 per 100 person-years of adults treated; 0.07, 0.04-0.13, p<0.0001). INTERPRETATION: Expansion of access to ART and co-trimoxazole prophylaxis could substantially reduce mortality and orphanhood among adults with HIV and their families living in resource-poor settings.

Cost-effectiveness of cotrimoxazole prophylaxis among persons with HIV in Uganda.

BACKGROUND: Daily prophylaxis with trimethoprim-sulfamethoxazole (cotrimoxazole) by persons with HIV reduces morbidity and mortality and is recommended by Joint United Nations Program on HIV/AIDS and World Health Organization (WHO), but there are limited published cost-effectiveness data for this intervention. We assessed the cost-effectiveness of cotrimoxazole prophylaxis for persons living with HIV in rural Uganda. METHODS: We modeled the cost-effectiveness of daily cotrimoxazole prophylaxis based on clinical results and operational data from a prospective cohort study of home-based care delivery to adults and children with HIV in rural Uganda who were older than the age of 5 years. Main outcome measures were net program cost and disability-adjusted life-years (DALYs) gained. We examined the provision of cotrimoxazole prophylaxis for (A) all HIV-infected individuals regardless of immunologic or clinical criteria; (B) those with WHO stage 2 or more advanced disease; (C) those with CD4 cell counts <500 cells/microL; and (D) those meeting criteria B or C, the current WHO recommendation. We calculated the costs and effectiveness of these 4 screening algorithms compared with no cotrimoxazole prophylaxis and calculated incremental cost-effectiveness ratios. We performed univariate and multivariate sensitivity analyses. RESULTS: Cotrimoxazole prophylaxis for all HIV-infected individuals (algorithm A) produced 7.3 life-years and 7.55 DALYs per 100 persons over 1 year compared with no prophylaxis. Using this screening algorithm, the intervention saved $2.50 per person-year. The program costs and the DALYs gained by algorithms A, B, and D were more favorable than those for algorithm C. Among algorithms A, B, and D, strategies using screening algorithms for WHO stage or CD4 cell counts were more costly and marginally less effective than providing cotrimoxazole prophylaxis to all HIV-infected individuals. CONCLUSIONS: Daily cotrimoxazole prophylaxis for HIV-infected individuals is highly cost-effective in rural Uganda. The use of screening algorithms to identify individuals with advanced HIV disease may result in higher program costs and less favorable cost-effectiveness.

Effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine-resistant malaria parasites among HIV-uninfected household members.

The purpose of this prospective cohort study was to assess the effect of cotrimoxazole prophylaxis taken by human immunodeficiency virus (HIV)-infected persons on the selection of sulfadoxine-pyrimethamine (SP)-resistant malaria parasites among HIV-uninfected household members. A total of 2,567 HIV-uninfected persons from 605 households were followed and blood specimens were collected each time an episode of Plasmodium falciparum malaria was diagnosed. Study participants were living in households where HIV-infected persons were either taking (exposed) or not taking (unexposed) cotrimoxazole prophylaxis. From all malaria episodes diagnosed, 50% of the specimens were randomly selected and tested for the presence of five key mutations known to mediate resistance to SP (dihydrofolate reductase [dhfr] Asn-108, Ile-51, and Arg-59, and dihydropteroate synthase [dhps] Gly-437 and Glu-540). Plasmodium falciparum isolates were recovered from 163 specimens in the exposed households and 113 specimens in the unexposed households, with similar proportions containing the dhfr triple mutant (37% versus 45%; P = 0.18), the dhps double mutant (64% versus 62%; P = 0.81), and the dhfr/dhps quintuple mutant (30% versus 32%; P = 0.74). The HIV-uninfected persons living with HIV-infected household members taking cotrimoxazole prophylaxis had a lower incidence of malaria (incidence rate ratio [IRR] = 0.64, 95% confidence interval [CI] = 0.50-0.83, P = 0.001) and fewer malaria episodes due to parasites containing the dhfr/dhps quintuple mutant (IRR = 0.61, 95% CI = 0.41-0.91, P = 0.014). Cotrimoxazole prophylaxis taken by HIV-infected persons did not select for SP-resistant malaria parasites among HIV-uninfected household members, and was associated with a lower overall incidence of SP-resistant malaria among household members.

Cost-effectiveness of home-based chlorination and safe water storage in reducing diarrhea among HIV-affected households in rural Uganda.

Safe water systems (SWSs) have been shown to reduce diarrhea and death. We examined the cost-effectiveness of SWS for HIV-affected households using health outcomes and costs from a randomized controlled trial in Tororo, Uganda. SWS was part of a home-based health care package that included rapid diarrhea diagnosis and treatment of 196 households with relatively good water and sanitation coverage. SWS use averted 37 diarrhea episodes and 310 diarrhea-days, representing 0.155 disability-adjusted life year (DALY) gained per 100 person-years, but did not alter mortality. Net program costs were 5.21 dollars/episode averted, 0.62 dollars/diarrhea-day averted, and 1,252 dollars/DALY gained. If mortality reduction had equaled another SWS trial in Kenya, the cost would have been 11 dollars/DALY gained. The high SWS cost per DALY gained was probably caused by a lack of mortality benefit in a trial designed to rapidly treat diarrhea. SWS is an effective intervention whose cost-effectiveness is sensitive to diarrhea-related mortality, diarrhea incidence, and effective clinical management.

Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study.

BACKGROUND: HIV-1 and malaria are common infections in Africa, and cause substantial morbidity and mortality. HIV infection has been associated with an increased incidence of malaria, and more severe disease. Our aim was to assess the effect of antiretroviral treatment (ART) on the frequency of clinical malaria in people with HIV, and to measure the additive effects of co-trimoxazole (trimethoprim and sulfamethoxazole) prophylaxis, ART, and insecticide-treated bednets. METHODS: In 2001, we enrolled 466 HIV-infected individuals aged 18 years or older in Uganda in a prospective cohort study that provided co-trimoxazole prophylaxis to 399 participants after 5 months of no intervention. In 2003, we enrolled 138 survivors from the initial study, and 897 new participants from the same community, to take antiretroviral therapy (ART) in addition to co-trimoxazole prophylaxis. The ART was in most cases a combination of stavudine, lamivudine, and nevirapine or efavirenz. In 2004, we also gave participants insecticide-treated bednets. Households were visited weekly by study staff to record fever, illness, or death in the preceding 7 days. In cases of reported fever in the previous 2 days, we took blood to test for malaria parasites. We compared the frequency of clinical malaria, adjusting for CD4-cell count, age, sex, and season. FINDINGS: 1035 individuals were given co-trimoxazole and ART (median age 38 years, 74% female, and median CD4-cell count 124 cells/microL); 985 of these, plus four new participants, received co-trimoxazole, ART, and bednets. There were 166 cases of clinical malaria in the study. Compared with a baseline malaria incidence of 50.8 episodes per 100 person-years, co-trimoxazole prophylaxis was associated with 9.0 episodes per 100 person-years (adjusted incidence rate ratio [IRR] 0.24, 95% CI 0.15-0.38); ART and co-trimoxazole with 3.5 episodes per 100 person-years (0.08, 0.04-0.17); and co-trimoxazole, ART, and bednets with 2.1 episodes per 100 person-years (0.05, 0.03-0.08). Malaria incidence was significantly lower during ART and co-trimoxazole than during co-trimoxazole alone (IRR 0.36 [95% CI 0.18-0.74], p=0.0056). INTERPRETATION: A combination of co-trimoxazole, antiretroviral therapy, and insecticide-treated bednets substantially reduced the frequency of malaria in adults with HIV.

Effect of home-based water chlorination and safe storage on diarrhea among persons with human immunodeficiency virus in Uganda.

Diarrhea is frequent among persons infected with human immunodeficiency virus (HIV) but few interventions are available for people in Africa. We conducted a randomized controlled trial of a home-based, safe water intervention on the incidence and severity of diarrhea among persons with HIV living in rural Uganda. Between April 2001 and November 2002, households of 509 persons with HIV and 1,521 HIV-negative household members received a closed-mouth plastic container, a dilute chlorine solution, and hygiene education (safe water system [SWS]) or simply hygiene education alone. After five months, HIV-positive participants received daily cotrimoxazole prophylaxis (160 mg of trimethoprim and 800 mg of sulfamethoxazole) and were followed for an additional 1.5 years. Persons with HIV using SWS had 25% fewer diarrhea episodes (adjusted incidence rate ratio [IRR] = 0.75, 95% confidence interval [CI] = 0.59-0.94, P = 0.015), 33% fewer days with diarrhea (IRR = 0.67, 95% CI = 0.48-0.94, P = 0.021), and less visible blood or mucus in stools (28% versus 39%; P < 0.0001). The SWS was equally effective with or without cotrimoxazole prophylaxis (P = 0.73 for interaction), and together they reduced diarrhea episodes by 67% (IRR = 0.33, 95% CI = 0.24-0.46, P < 0.0001), days with diarrhea by 54% (IRR = 0.46, 95% CI = 0.32-0.66, P < 0.0001), and days of work or school lost due to diarrhea by 47% (IRR = 0.53, 95% CI = 0.34-0.83, P < 0.0056). A home-based safe water system reduced diarrhea frequency and severity among persons with HIV living in Africa and large scale implementation should be considered.