Community perceptions, acceptability, and the durability of house screening interventions against exposure to malaria vectors in Nyimba district, Zambia.

BACKGROUND: House screening remains conspicuously absent in national malaria programs despite its recognition by the World Health Organization as a supplementary malaria vector-control intervention. This may be attributed, in part, to the knowledge gap in screen durability or longevity in local climatic conditions and community acceptance under specific cultural practices and socio-economic contexts. The objectives of this study were to assess the durability of window and door wire mesh screens a year after full house screening and to assess the acceptability of the house screening intervention to the participants involved. METHODS: This study was conducted in Nyimba district, Zambia and used both quantitative and qualitative methods of data collection and analysis. Both direct observation and questionnaires were employed to assess the durability of the screens and the main reasons for damage. Findings on damage were summarized as percentages. Focus group discussions were used to assess people's knowledge, perceptions, and acceptability of the closing eaves and house screening intervention. Deductive coding and inductive coding were used to analyse the qualitative data. RESULTS: A total of 321 out of 400 (80.3%) household owners of screened houses were interviewed. Many window screens (90.3%) were intact. In sharp contrast, most door screens were torn (n = 150; 46.7%) or entirely removed (n = 55; 17.1%). Most doors (n = 114; 76%) had their wire mesh damaged or removed on the bottom half. Goats (25.4%), rust (17.6%) and children (17.1%) were cited most as the cause of damage to door screens. The focus group discussion elicited positive experiences from the participants following the closing of eaves and screening of their windows and doors, ranging from sleeping peacefully due to reduced mosquito biting and/or nuisance and having fewer insects in the house. Participants linked house screening to reduced malaria in their households and community. CONCLUSION: This study demonstrated that in rural south-east Zambia, closing eaves and screening windows and doors was widely accepted. Participants perceived that house screening reduced human-vector contact, reduced the malaria burden and nuisance biting from other potentially disease carrying insects. However, screened doors are prone to damage, mainly by children, domestic animals, rust, and termites.

Evaluation of the Acute flaccid paralysis surveillance indicators in Zambia from 2015-2021: a retrospective analysis.

BACKGROUND: The resurgence of poliovirus infection in previously polio free regions and countries calls for renewed commitment to the global polio eradication efforts including strengthening of Acute Flaccid Paralysis (AFP) surveillance systems. Zambia is one of the countries substantially at risk for the importation of poliovirus infection from neighbouring countries including Malawi, Mozambique, and Democratic Republic of the Congo (DRC). This study describes a seven-year AFP surveillance, assesses the surveillance indicators, and highlights areas for improvement. METHODS: We conducted retrospective analysis of the routinely collected AFP surveillance data from January 2015 to December 2022. The AFP surveillance indicators performance was assessed using the World Health Organisation's recommended minimum AFP surveillance indicators performance. RESULTS: Cumulatively, a total of 1715 AFP cases were reported over the study period. More than half, 891 (52%) of reported cases were aged < 5 years with 917 (53.5%) of males. More than half, 1186 (69.2%) had fever at onset, 718 (41.9%) had asymmetric paralysis and 1164 (67.9%) had their paralysis progressed within 3 days of onset. The non-polio AFP rate ranges from 3.4 to 6.4 per 100,000 children < 15 years old and stool adequacy ranging from 70.9% to 90.2% indicating sensitive surveillance with late detection of cases. The percentage of cases with early stool collection, timely transportation was above the World Health Organisation (WHO) minimum of 80% but with declining proportion of stools arriving in the laboratory in optimal condition. Completeness of 60-days follow-up evaluation was suboptimal ranging from 0.9% to 28.2%. CONCLUSION: The AFP surveillance system in Zambia is doing well. However, additional efforts are needed to improve early detection of cases; stool sample collection, transportation and monitoring to ensure arrival in good condition in the laboratory; and improve 60-days follow-up evaluation for evidenced-based classification of inadequate AFP cases and proper care.

Cholera Epidemic - Lusaka, Zambia, October 2017-May 2018.

On October 6, 2017, an outbreak of cholera was declared in Zambia after laboratory confirmation of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, from stool specimens from two patients with acute watery diarrhea. The two patients had gone to a clinic in Lusaka, the capital city, on October 4. Cholera cases increased rapidly, from several hundred cases in early December 2017 to approximately 2,000 by early January 2018 (Figure). In collaboration with partners, the Zambia Ministry of Health (MoH) launched a multifaceted public health response that included increased chlorination of the Lusaka municipal water supply, provision of emergency water supplies, water quality monitoring and testing, enhanced surveillance, epidemiologic investigations, a cholera vaccination campaign, aggressive case management and health care worker training, and laboratory testing of clinical samples. In late December 2017, a number of water-related preventive actions were initiated, including increasing chlorine levels throughout the city's water distribution system and placing emergency tanks of chlorinated water in the most affected neighborhoods; cholera cases declined sharply in January 2018. During January 10-February 14, 2018, approximately 2 million doses of oral cholera vaccine were administered to Lusaka residents aged ≥1 year. However, in mid-March, heavy flooding and widespread water shortages occurred, leading to a resurgence of cholera. As of May 12, 2018, the outbreak had affected seven of the 10 provinces in Zambia, with 5,905 suspected cases and a case fatality rate (CFR) of 1.9%. Among the suspected cases, 5,414 (91.7%), including 98 deaths (CFR = 1.8%), occurred in Lusaka residents.

The reported impact of non-communicable disease investment cases in 13 countries.

Non-communicable diseases (NCDs) are a leading health and development challenge worldwide. Since 2015, WHO and the United Nations Development Programme have provided support to governments to develop national NCD investment cases to describe the socioeconomic dimensions of NCDs. To assess the impact of the investment cases, semistructured interviews and a structured process for gathering written feedback were conducted between July and October 2022 with key informants in 13 countries who had developed a national NCD investment case between 2015 and 2020. Investment cases describe: (1) the social and economic costs of NCDs, including their distribution and projections over time; (2) priority areas for scaled up action; (3) the cost and returns from investing in WHO-recommended measures to prevent and manage NCDs; and (4) the political dimensions of NCD responses. While no country had implemented all the recommendations set out in their investment case reports, actions and policy changes attributable to the investment cases were identified, across (1) governance; (2) financing; and (3) health service access and delivery. The pathways of these changes included: (1) stronger collaboration across government ministries and partners; (2) advocacy for NCD prevention and control; (3) grounding efforts in nationally owned data and evidence; (4) developing mutually embraced 'language' across health and finance; and (5) elevating the priority accorded to NCDs, by framing action as an investment rather than a cost. The assessment also identified barriers to progress on the investment case implementation, including the influence of some private sector entities on sectors other than health, the impact of the COVID-19 pandemic, and changes in senior political and technical government officials. The results suggest that national NCD investment cases can significantly contribute to catalysing the prevention and control of NCDs through strengthening governance, financing, and health service access and delivery.

Lymphatic Filariasis Elimination Status: Wuchereria bancrofti Infections in Human Populations after Five Effective Rounds of Mass Drug Administration in Zambia.

Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted via a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia, whose predilection site is the lymphatic system. The damage to the lymph system causes swelling in the legs, arms, and genitalia. A mapping survey conducted between 2003 and 2011 determined LF as being endemic in Zambia in 96 out of 116 districts. Elimination of LF is known to be possible by stopping the spread of the infection through large-scale preventive chemotherapy. Therefore, mass drug administration (MDA) with diethylcarbamazine citrate (DEC) (6 mg/kg) and Albendazole (400 mg) for Zambia has been conducted and implemented in all endemic districts with five effective rounds. In order to determine whether LF prevalence has been sufficiently reduced to levels less than 2% antigenemia and less than 1% microfilaremia, a pre-transmission assessment survey (pre-TAS) was conducted. Therefore, post-MDA pre-TAS was conducted between 2021 and 2022 in 80 districts to determine the LF prevalence. We conducted a cross-sectional seroprevalence study involving 600 participants in each evaluation unit (EU) or each district. The study sites (sentinel and spot-check sites) were from districts that were the implementation units (IUs) of the LF MDA. These included 80 districts from the 9 provinces. A total of 47,235 people from sentinel and spot-check locations were tested. Of these, valid tests were 47,052, of which 27,762 (59%) were females and 19,290 (41%) were males. The survey revealed in the 79/80 endemic districts a prevalence of Wb antigens of 0.14% and 0.0% prevalence of microfilariae. All the surveyed districts had an optimum prevalence of less than 2% for antigenaemia, except for Chibombo district. The majority of participants that tested positive for Wuchereria bancrofti (Wb) Antigens (Ag) were those that had 2, 3, and 4 rounds of MDA. Surprisingly, individuals that had 1 round of MDA were not found to have circulating antigens of Wb. The study showed that all the surveyed districts, except for Chibombo, passed pre-TAS. This further implies that there is a need to conduct transmission assessment surveys (TASs) in these districts.

Euvichol-plus vaccine campaign coverage during the 2017/2018 cholera outbreak in Lusaka district, Zambia: a cross-sectional descriptive study.

OBJECTIVE: To determine the coverage for the oral cholera vaccine (OCV) campaign conducted during the 2017/2018 cholera outbreak in Lusaka, Zambia. STUDY DESIGN: A descriptive cross-sectional study employing survey method conducted among 1691 respondents from 369 households following the second round of the 2018 OCV campaign. STUDY SETTING: Four primary healthcare facilities and their catchment areas in Lusaka city (Kanyama, Chawama, Chipata and Matero subdistricts). PARTICIPANTS: A total of 1691 respondents 12 months and older sampled from 369 households where the campaign was conducted. A satellite map-based sampling technique was used to randomly select households. DATA MANAGEMENT AND ANALYSIS: A pretested electronic questionnaire uploaded on an electronic tablet (ODK V.1.12.2) was used for data collection. Descriptive statistics were computed to summarise respondents' characteristics and OCV coverage per dose. Bivariate analysis (χ2 test) was conducted to stratify OCV coverage according to age and sex for each round (p<0.05). RESULTS: The overall coverage for the first, second and two doses were 81.3% (95% CI 79.24% to 83.36%), 72.1% (95% CI 69.58% to 74.62%) and 66% (95% CI 63.22% to 68.78%), respectively. The drop-out rate was 18.8% (95% CI 14.51% to 23.09%). Of the 81.3% who received the first dose, 58.8% were female. Among those who received the second dose, the majority (61.0%) were females aged between 5 and 14 years (42.6%) and 15 and 35 years (27.7%). Only 15.5% of the participants aged between 36 and 65 and 2.5% among those aged above 65 years received the second dose. CONCLUSION: These findings confirm the 2018 OCV campaign coverage and highlight the need for follow-up surveys to validate administrative coverage estimates using population-based methods. Reliance on health facility data alone may mask low coverage and prevent measures to improve programming. Future public health interventions should consider sociodemographic factors in order to achieve optimal vaccine coverage.

Effectiveness of two doses of Euvichol-plus oral cholera vaccine in response to the 2017/2018 outbreak: a matched case-control study in Lusaka, Zambia.

INTRODUCTION: Zambia experienced a major cholera outbreak in 2017-2018, with more than 5905 cases reported countrywide, predominantly from the peri-urban slums of Lusaka city. The WHO recommends the use of oral cholera vaccines (OCVs) together with traditional control measures, including health promotion, provision of safe water and improving sanitation, in cholera endemic areas and during cholera outbreaks. In response to this outbreak, the Zambian government implemented the OVC campaign and administered the Euvichol-plus vaccine in the high-risk subdistricts of Lusaka. Although OCVs have been shown to be effective in preventing cholera infection in cholera endemic and outbreak settings, the effectiveness of the Euvichol-plus vaccine has not yet been evaluated in Zambia. This study aimed to determine the effectiveness of two doses of OCV administered during the 2017/2018 vaccination campaign. METHODS: We conducted a matched case-control study involving 79 cases and 316 controls following the mass vaccination campaign in the four subdistricts of Lusaka (Chawama, Chipata, Kanyama and Matero). Matching of controls was based on the place of residence, age and sex. Conditional logistic regression was used for analysis. Adjusted OR (AOR), 95% CI and vaccine effectiveness (1-AOR) for two doses of Euvichol-plus vaccine and any dose were estimated (p<0.05). RESULTS: The AOR vaccine effectiveness for two doses of Euvichol-plus OCV was 81.0% (95% CI 66.0% to 78.0%; p<0.01). Secondary analysis showed that vaccine effectiveness for any dose was 74.0% (95% CI 50.0% to 86.0%; p<0.01). CONCLUSION: These findings show that two doses of Euvichol-plus OCV are effective in a cholera outbreak setting in Lusaka, Zambia. The findings also indicate that two doses are more effective than a single dose and thus support the use of two doses of the vaccine as part of an integrated intervention to cholera control during outbreaks.

Estimating trends in the burden of malaria at country level.

National disease burdens are often not estimated at all or are estimated using inaccurate methods, partly because the data sources for assessing disease burden-nationally representative household surveys, demographic surveillance sites, and routine health information systems-each have their limitations. An important step forward would be a more consistent quantification of the population at risk of malaria. This is most likely to be achieved by delimiting the geographical distribution of malaria transmission using routinely collected data on confirmed cases of disease. However, before routinely collected data can be used to assess trends in the incidence of clinical cases and deaths, the incompleteness of reporting and variation in the utilization of the health system must be taken into account. In the future, sentinel surveillance from public and private health facilities, selected according to risk stratification, combined with occasional household surveys and other population-based methods of surveillance, may provide better assessments of malaria trends.

Viewpoint: evaluating the impact of malaria control efforts on mortality in sub-Saharan Africa.

OBJECTIVE: To describe an approach for evaluating the impact of malaria control efforts on malaria-associated mortality in sub-Saharan Africa, where disease-specific mortality trends usually cannot be measured directly and most malaria deaths occur among young children. METHODS: Methods for evaluating changes in malaria-associated mortality are examined; advantages and disadvantages are presented. RESULTS: All methods require a plausibility argument-i.e., an assumption that mortality reductions can be attributed to programmatic efforts if improvements are found in steps of the causal pathway between intervention scale-up and mortality trends. As different methods provide complementary information, they can be used together. We recommend following trends in the coverage of malaria control interventions, other factors influencing childhood mortality, malaria-associated morbidity (especially anaemia), and all-cause childhood mortality. This approach reflects decreases in malaria's direct and indirect mortality burden and can be examined in nearly all countries. Adding other information can strengthen the plausibility argument: trends in indicators of malaria transmission, information from demographic surveillance systems and sentinel sites where malaria diagnostics are systematically used, and verbal autopsies linked to representative household surveys. Health facility data on malaria deaths have well-recognized limitations; however, in specific circumstances, they could produce reliable trends. Model-based predictions can help describe changes in malaria-specific burden and assist with program management and advocacy. CONCLUSIONS: Despite challenges, efforts to reduce malaria-associated mortality in Africa can be evaluated with trends in malaria intervention coverage and all-cause childhood mortality. Where there are resources and interest, complementary data on malaria morbidity and malaria-specific mortality could be added.

Artemisinin versus nonartemisinin combination therapy for uncomplicated malaria: randomized clinical trials from four sites in Uganda.

BACKGROUND: Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. METHODS AND FINDINGS: We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ) + sulfadoxine-pyrimethamine (SP); amodiaquine (AQ) + SP; or AQ + artesunate (AS). Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84%) were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p < 0.01) after AQ + SP or AQ + AS (7%-18% and 4%-12%, respectively). Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection) was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, p < 0.003). CONCLUSION: AQ + AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy. The registration number for this trial is ISRCTN67520427 (http://www.controlled-trials.com/isrctn/trial/|/0/67520427.html).

Distinguishing recrudescences from new infections in antimalarial clinical trials: major impact of interpretation of genotyping results on estimates of drug efficacy.

The use of molecular genotyping to distinguish recrudescence from new infections has become common in antimalarial clinical trials. However, methods used to interpret genotyping results have not been standardized. We analyzed data from 3,000 patients enrolled in clinical trials at seven sites in Uganda. Late treatment failure requiring genotyping occurred in 51% of the patients. Among samples successfully genotyped, 21% were definitive new infections (no recrudescent strains present on day of failure), 35% were definitive recrudescences (only recrudescent strains present), and 44% were mixed (new and recrudescent strains present). The probability of having a mixed genotyping result increased as transmission intensity increased. At the highest transmission site, the estimated risk of treatment failure increased from 34% to 84% for chloroquine plus sulfadoxine-pyrimethamine, from 18% to 45% for amodiaquine plus sulfadoxine-pyrimethamine, and from 12% to 57% for amodiaquine plus artesunate, depending on whether mixed genotyping results were classified as new infections or recrudescences, respectively. The method used to classify treatment outcomes can have a major impact on estimates of drug efficacy, especially in areas of high transmission intensity.

Sulfadoxine-pyrimethamine plus chloroquine or amodiaquine for uncomplicated falciparum malaria: a randomized, multisite trial to guide national policy in Uganda.

The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine-pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-pyrimethamine and from 13% to 35% with amodiaquine plus sulfadoxine-pyrimethamine (risk differences 21-32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-pyrimethamine was significantly more efficacious; however, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen.

IDSR as a platform for implementing IHR in African countries.

Of the 46 countries in the World Health Organization (WHO) African region (AFRO), 43 are implementing Integrated Disease Surveillance and Response (IDSR) guidelines to improve their abilities to detect, confirm, and respond to high-priority communicable and noncommunicable diseases. IDSR provides a framework for strengthening the surveillance, response, and laboratory core capacities required by the revised International Health Regulations [IHR (2005)]. In turn, IHR obligations can serve as a driving force to sustain national commitments to IDSR strategies. The ability to report potential public health events of international concern according to IHR (2005) relies on early warning systems founded in national surveillance capacities. Public health events reported through IDSR to the WHO Emergency Management System in Africa illustrate the growing capacities in African countries to detect, assess, and report infectious and noninfectious threats to public health. The IHR (2005) provide an opportunity to continue strengthening national IDSR systems so they can characterize outbreaks and respond to public health events in the region.

Effect of HIV-1 infection on antimalarial treatment outcomes in Uganda: a population-based study.

BACKGROUND: Human immunodeficiency virus (HIV) infection may increase the burden of malaria by increasing susceptibility to infection or by decreasing the response to antimalarial treatment. We investigated the seroprevalence rate of HIV-1 infection and its effect on antimalarial treatment outcomes in adults and children with uncomplicated falciparum malaria in Uganda. METHODS: This retrospective study included 1965 patients > or =18 months old who were randomized to receive 1 of 3 antimalarial regimens at 7 sites in Uganda. HIV-1 testing was performed using 2 enzyme-linked immunosorbent assays and Western blot analysis of stored blood spots. The primary study outcome was clinical treatment failure at 28 days after antimalarial treatment. Molecular genotyping was used to distinguish clinical treatment failures due to new infections from those due to recrudescences. RESULTS: The HIV-1 seroprevalence rate was 2.5% in 1802 patients <18 years old and 31% in 163 patients > or =18 years old presenting with malaria. HIV-1 infection was associated with a >3-fold (hazard ratio [HR], 3.28 [95% confidence interval [CI], 1.25-8.59]) increased risk of clinical treatment failure for adults, but there was no increased risk for HIV-1-infected children. Molecular genotyping revealed that clinical treatment failures were due to new infections (HR, 6.35 [95% CI, 1.64-24.5]) rather than to recrudescences (HR, 1.51 [95% CI, 0.27-8.58]). CONCLUSIONS: The HIV-1 seroprevalence rate was surprisingly high in adults presenting with malaria. This finding supports the implementation of routine HIV counseling and testing for adults with uncomplicated falciparum malaria. HIV-1 infection increased the susceptibility to new malarial infections but did not increase the risk of recrudescences in adults.

Artemisinin combination therapies for treatment of uncomplicated malaria in Uganda.

OBJECTIVES: To compare the efficacy and safety of artemisinin combination therapies for the treatment of uncomplicated falciparum malaria in Uganda. DESIGN: Randomized single-blind controlled trial. SETTING: Tororo, Uganda, an area of high-level malaria transmission. PARTICIPANTS: Children aged one to ten years with confirmed uncomplicated P. falciparum malaria. INTERVENTIONS: Amodiaquine + artesunate or artemether-lumefantrine. OUTCOME MEASURES: Risks of recurrent symptomatic malaria and recurrent parasitemia at 28 days, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections. RESULTS: Of 408 participants enrolled, 403 with unadjusted efficacy outcomes were included in the per-protocol analysis. Both treatment regimens were highly efficacious; no recrudescences occurred in patients treated with amodiaquine + artesunate, and only two occurred in those treated with artemether-lumefantrine. However, recurrent malaria due to new infections was common. The unadjusted risk of recurrent symptomatic malaria was significantly lower for participants treated with artemether-lumefantrine than for those treated with amodiaquine + artesunate (27% versus 42%, risk difference 15%, 95% CI 5.9%-24.2%). Similar results were seen for the risk of recurrent parasitemia (51% artemether-lumefantrine versus 66% amodiaquine + artesunate, risk difference 16%, 95% CI 6.2%-25.2%). Amodiaquine + artesunate and artemether-lumefantrine were both well-tolerated. Serious adverse events were uncommon with both regimens. CONCLUSIONS: Amodiaquine + artesunate and artemether-lumefantrine were both highly efficacious for treatment of uncomplicated malaria. However, in this holoendemic area, despite the excellent performance of both regimens in terms of efficacy, many patients experienced recurrent parasitemia due to new infections. Artemether-lumefantrine was superior to amodiaquine + artesunate for prevention of new infections. To maximize the benefit of artemisinin combination therapy in Africa, treatment should be integrated with strategies to prevent malaria transmission. The impact of frequent repeated therapy on the efficacy, safety, and cost-effectiveness of new artemisinin regimens should be further investigated.

Quality of parental consent in a Ugandan malaria study.

OBJECTIVES: We surveyed Ugandan parents who enrolled their children in a randomized pediatric malaria treatment trial to evaluate the parents' levels of understanding about the treatment trial and the quality of the parents' consents to allow their children to participate in the study. METHODS: We conducted 347 interviews immediately following enrollment at 4 Ugandan sites. RESULTS: A majority (78%) of the parents, most of whom where mothers (86%) had at most a primary school education. Of the participating mothers, a substantial percentage reported that they remembered being told about the study's purpose (77%), the required number of visits (88%), the risks involved (61%), treatment allocation (84%), and their ability to discontinue their children's participation (64%). In addition, most reported knowing the trial's purpose (80%) and the required number of visits (78%); however, only 18% could name possible side effects from the drugs being administered, and only 19% knew that children would not all be administered identical treatments. Ninety-four percent reported that they made the enrollment decision themselves, but 58% said they felt pressure to participate because of their child's illness, and 15% said they felt some type of pressure to participate from others; 41% reported knowing that they did not have to participate. CONCLUSIONS: The consent Ugandan parents provided to allow their children to participate in the malaria study was of mixed quality. Parents understood many of the study details, but they were not very aware of the risks involved or of randomization. Many parents felt that they could not have refused to participate because their child was sick and they either did not know or did not believe that their child would receive treatment outside of the study. Our results indicate that further debate is needed about informed consent in treatment studies of emergent illnesses in children.

Health-seeking behavior for malaria among child and adult headed households in Rakai district, Uganda.

BACKGROUND: The number of orphans in Rakai district, Uganda is estimated to be 34,902 (OCBO, 2000) which translates into 28% of children under the age of 18 years. Young people who have been orphaned and as a result became heads of households must look after themselves and their siblings. These children are likely to be faced with several health problems and have to take crucial life decisions without parental/adult guidance. OBJECTIVES: This study was conducted in order to understand how child-headed households, Rakai district in Uganda recognize malaria, their health-seeking behavior when malaria is suspected and reasons for the type of behavior compared to the adult-headed households. METHODS: A comparative cross-sectional study was conducted in 300 households in Rakai district, Uganda, in which 8/23 (35%) of sub-counties and 150 child-headed households were included. The closest neighborhood adult-headed household to each child-headed household was selected for comparison. Individual interview was carried out with the respondents using semi-structure questionnaire. Key informant interview and focus group discussions were also conducted. RESULTS: The main findings were that the respondents in child-headed households had less knowledge on signs and symptoms of simple and severe malaria compared to adult heads of households. Respondents in child-headed households were less likely to seek health care from health facilities (OR=0.59, CI=0.36-0.97, p-value=0.028). There was no significant difference in the time lag before taking first action in the two types of households (OR=0.72, CI=0.42-1.22, p-value=0.194). The respondents in child-headed households were six times (OR=5.70,CI=2.75-11.91, p-value<0.001) more likely to use local herb for treatment of malaria than the adult heads households. Major reasons stated by the respondents for choosing where health care is sought included distance to source of health care, cheap or free treatment, availability of drugs, and quick services to patients. CONCLUSION: The respondents in child-headed households had less knowledge on signs and symptoms of simple and severe malaria and receive too little or late health care from health professionals compared to the adult heads of households probably due to lack of knowledge and money. Information Communication and Education programs should be designed and target the child-headed households and supply home packs.

Antimalarial efficacy of sulfadoxine-pyrimethamine, amodiaquine and a combination of chloroquine plus sulfadoxine-pyrimethamine in Bundi Bugyo, western Uganda.

We report below an in vivo antimalarial efficacy study conducted in 2002 in Bundi Bugyo, a district of western Uganda housing a large displaced population. We tested sulfadoxine-pyrimethamine (SP), amodiaquine (AQ) and the combination chloroquine plus SP (CQ + SP). A total of 268 children with uncomplicated Plasmodium falciparum malaria were followed-up for 28 days according to WHO recommendations, with PCR genotyping to distinguish late recrudescences from re-infections. PCR-adjusted failure proportions at day 28 were 37.0% (34/92, 95% CI 27.1-47.7) in the SP group, 20.6% (14/68, 95% CI 11.7-32.1) in the AQ group and 22.8% (18/79, 95% CI 14.1-33.6) in the CQ + SP group. Early failures were particularly frequent in the SP group (15.2%). Clearance of gametocytes was slower in the SP and CQ + SP groups than in the AQ group. This study suggests that, in Bundi Bugyo, CQ + SP (Uganda's first-line regimen) will need to be replaced by a more efficacious regimen. Across Uganda, the deployment of SP containing combinations may not be a feasible long-term strategy. For Bundi Bugyo, we recommend a combination of artesunate and AQ. Our study also confirms previous findings that resistance is considerably underestimated by 14-day follow-ups. Antimalarial policy decisions should therefore be based on 28-day studies, with PCR adjustment to distinguish re-infections.

Efficacy of sulphadoxine-pyrimethamine alone or combined with amodiaquine or chloroquine for the treatment of uncomplicated falciparum malaria in Ugandan children.

The rapid development of falciparum resistance to sulphadoxine-pyrimethamine (SP) in East and Central Africa has raised concerns as to the efficacy of combining it with another drug. In 2002, we assessed the efficacy of SP alone and combined with amodiaquine (AQ/SP) or chloroquine (CQ/SP) in Ugandan children with uncomplicated falciparum malaria. At day 14, adequate clinical response was 100% (84/84) for AQ/SP, 93% (92/101) for CQ/SP and 91% (73/80) for SP. At day 28, parasitological failure (RI-RIII) occurred in 16% (13/80) of children treated with AQ/SP, in 48% (48/100) of those treated with CQ/SP and in 61% (48/79) of those treated with SP alone. Compared with the AQ/SP arm, the odds for parasitological failure at day 28 were five times higher (95% CI, 2-10) in the CQ/SP group and sevenfold higher (95% CI, 3-17) in that of SP alone. CQ/SP does not offer any significant added benefit over SP alone while AQ/SP is an efficacious low-cost combination. These findings have important policy implications for Uganda and other resource-constrained African countries faced with the problematic choice of a new first-line antimalarial treatment in a context of high CQ resistance.