Knowledge, attitudes, and practices of health care waste management among Zambian health care workers.

Poor management of health care waste poses a serious threat to the health of health care workers, patients and communities. In developing countries, adequate health care waste management (HCWM) is often a challenge. To address this, the Zambian Health Services Improvement Project with HCWM as a component, was implemented in five Zambian provinces (Luapula, Muchinga, Northern, North-Western and Western Provinces), under which this cross-sectional study was conducted to identify the knowledge, attitudes, and practices of health care workers on HCWM. Fifty government hospitals and health posts from five provinces in Zambia were included in the study. Data was collected using a mixed-methods approach, which included surveys with health care workers (n = 394), in-depth interviews (n = 47) with health officials at the provincial, district, and facility levels, and observational checklists (n = 86). Overall, knowledge of proper waste segregation was average (mean knowledge score 4.7/ 7). HCWM knowledge varied significantly by job position (p = 0.02) and not by facility level, years of service, nor prior training. Only 37.3% of respondents recalled having received any sort of HCWM training. Poor waste segregation practice was found as only 56.9% of the facilities used an infectious waste bag (yellow, red or orange bin liner) and a black bag for general waste. This study revealed that only 43% of facilities had a functional incinerator on site for infectious waste treatment. Needle sticks were alarmingly high with 31.3% of all respondents reporting a prior needle stick. The system of HCWM remains below national and international standards in health facilities in Zambia. It is imperative that all health care workers undergo comprehensive HCWM training and sufficient health care waste commodities are supplied to all health facility levels in Zambia.

Reactive focal drug administration associated with decreased malaria transmission in an elimination setting: Serological evidence from the cluster-randomized CoRE study.

Efforts to eliminate malaria transmission need evidence-based strategies. However, accurately assessing end-game malaria elimination strategies is challenging due to the low level of transmission and the rarity of infections. We hypothesised that presumptively treating individuals during reactive case detection (RCD) would reduce transmission and that serology would more sensitively detect this change over standard approaches. We conducted a cluster randomised control trial (NCT02654912) of presumptive reactive focal drug administration (RFDA-intervention) compared to the standard of care, reactive focal test and treat (RFTAT-control) in Southern Province, Zambia-an area of low seasonal transmission (overall incidence of ~3 per 1,000). We measured routine malaria incidence from health facilities as well as PCR parasite prevalence / antimalarial seroprevalence in an endline cross-sectional population survey. No significant difference was identified from routine incidence data and endline prevalence by polymerase chain reaction (PCR) had insufficient numbers of malaria infections (i.e., 16 infections among 6,276 children) to assess the intervention. Comparing long-term serological markers, we found a 19% (95% CI = 4-32%) reduction in seropositivity for the RFDA intervention using a difference in differences approach incorporating serological positivity and age. We also found a 37% (95% CI = 2-59%) reduction in seropositivity to short-term serological markers in a post-only comparison. These serological analyses provide compelling evidence that RFDA both has an impact on malaria transmission and is an appropriate end-game malaria elimination strategy. Furthermore, serology provides a more sensitive approach to measure changes in transmission that other approaches miss, particularly in very low transmission settings. Trial Registration: Registered at www.clinicaltrials.gov (NCT02654912, 13/1/2016).

Impact of Four Rounds of Mass Drug Administration with Dihydroartemisinin-Piperaquine Implemented in Southern Province, Zambia.

Over the past decade, Zambia has made substantial progress against malaria and has recently set the ambitious goal of eliminating by 2021. In the context of very high vector control and improved access to malaria diagnosis and treatment in Southern Province, we implemented a community-randomized controlled trial to assess the impact of four rounds of community-wide mass drug administration (MDA) and household-level MDA (focal MDA) with dihydroartemisinin-piperaquine (DHAP) implemented between December 2014 and February 2016. The mass treatment campaigns achieved relatively good household coverage (63-79%), were widely accepted by the community (ranging from 87% to 94%), and achieved very high adherence to the DHAP regimen (81-96%). Significant declines in all malaria study end points were observed, irrespective of the exposure group, with the overall parasite prevalence during the peak transmission season declining by 87.2% from 31.3% at baseline to 4.0% in 2016 at the end of the trial. Children in areas of lower transmission (< 10% prevalence at baseline) that received four MDA rounds had a 72% (95% CI = 12-91%) reduction in malaria parasite prevalence as compared with those with the standard of care without any mass treatment. Mass drug administration consistently had the largest short-term effect size across study end points in areas of lower transmission following the first two MDA rounds. In the context of achieving very high vector control coverage and improved access to diagnosis and treatment for malaria, our results suggest that MDA should be considered for implementation in African settings for rapidly reducing malaria outcomes in lower transmission settings.

Recent Travel History and Plasmodium falciparum Malaria Infection in a Region of Heterogenous Transmission in Southern Province, Zambia.

As Zambia continues to reduce its malaria incidence and target elimination in Southern Province, there is a need to identify factors that can reintroduce parasites and sustain malaria transmission. To examine the relative contributions of types of human mobility on malaria prevalence, this analysis quantifies the proportion of the population having recently traveled during both peak and nonpeak transmission seasons over the course of 2 years and assesses the relationship between short-term travel and malaria infection status. Among all residents targeted by mass drug administration in the Lake Kariba region of Southern Province, 602,620 rapid diagnostic tests and recent travel histories were collected during four campaign rounds occurring between December 2014 and February 2016. Rates of short-term travel in the previous 2 weeks fluctuated seasonally from 0.3% to 1.2%. Travel was significantly associated with prevalent malaria infection both seasonally and overall (adjusted odds ratio [AOR]: 2.55; 95% CI: 2.28-2.85). The strength of association between travel and malaria infection varied by travelers' origin and destination, with those recently traveling to high-prevalence areas from low-prevalence areas experiencing the highest odds of malaria infection (AOR: 7.38). Long-lasting insecticidal net usage while traveling was associated with a relative reduction in infections (AOR: 0.74) compared with travelers not using a net. Although travel was directly associated with only a small fraction of infections, importation of malaria via human movement may play an increasingly important role in this elimination setting as transmission rates continue to decline.

Prevalence of Plasmodium falciparum and Non-falciparum Infections by Photo-Induced Electron Transfer-PCR in a Longitudinal Cohort of Individuals Enrolled in a Mass Drug Administration Trial in Southern Province, Zambia.

Malaria burden in Zambia has significantly declined over the last decade because of improved coverage of several key malaria interventions (e.g., vector control, case management, bed net distributions, and enhanced surveillance/responses). Campaign-based mass drug administration (MDA) and focal MDA (fMDA) were assessed in a trial in Southern Province, Zambia, to identify its utility in elimination efforts. As part of the study, a longitudinal cohort was visited and tested (by PCR targeting the 18s rRNA and a Plasmodium falciparum-specific rapid diagnostic test [RDT] from SD Bioline) every month for the trial duration (18 months). Overall, there was high concordance (> 97%) between the PCR and RDT results, using the PCR as the gold standard. The RDTs had high specificity and negative predictive values (98.5% and 98.6%, respectively) but low sensitivity (53.0%) and a low positive predictive value (53.8%). There was evidence for persistent antigenemia affecting the low specificity of the RDT, while false-negative RDTs were associated with a lower parasite density than true positive RDTs. Plasmodium falciparum was the dominant species identified, with 98.3% of all positive samples containing P. falciparum. Of these, 97.5% were mono-infections and 0.8% coinfections with one other species. Plasmodium malariae was found in 1.4% of all positive samples (50% mono-infections and 50% coinfections with P. falciparum), whereas Plasmodium ovale was found in 1.1% of all positive samples (90% mono-infections and 10% coinfections with P. falciparum). Although MDA/fMDA appeared to reduce P. malariae prevalence, P. ovale prevalence appeared unchanged.

Towards universal coverage for nutrition services in children under five years-A descriptive analysis of the capacity of level one hospitals to provide nutrition services in five provinces of Zambia.

BACKGROUND: Malnutrition continues to be a major public health challenge in Zambia. To effectively address this, health systems must be well strengthened to deliver an effective continuum of care. This paper examines health systems issues and services in relation to nutritional support to children under five years, in order to identify gaps and propose interventions towards universal coverage of essential nutrition services. METHODS: This analysis utilized data from a cross sectional mixed-methods study on factors associated with Severe Acute Malnutrition (SAM) in under-five children to assess health facility nutrition services on offer at select level-one hospitals in five out of ten provinces in Zambia. Stata version 13 was used for analysis. We conducted univariate analysis to assess nutrition services offered, functionality of equipment and tools, availability of human resource and human resource development, and availability of drugs used for assessment and management of nutrition-related health outcomes. RESULTS: We found large variations in the level of nutrition services on offer across districts and provinces. Eighty-eight percent of all the hospitals sampled provided group nutrition counseling and 92% of the hospitals in our sample offered individual nutrition counseling to their clients. Overall, the existence of referral and counter-referral systems between the Community Based Volunteers and hospitals were the lowest among all services assessed at 48% and 58% respectively. We also found inadequate numbers of human resource across all cadres with an exception of nutritionists as recommended by the Ministry of Health. CONCLUSIONS: This study has revealed a number of gaps in the health system and health service delivery that requires to be addressed; most notably, a lack of tools, policies and guidelines, drugs and health specialists to help care for malnourished infants and children. Our findings also reveal inadequate referral systems between the community and health facilities in the management of severe acute malnutrition. Achieving universal coverage for nutrition services in Zambia will require a lot more attention to the health systems issues found in this study.

Community-led Responses for Elimination (CoRE): a study protocol for a community randomized controlled trial assessing the effectiveness of community-level, reactive focal drug administration for reducing Plasmodium falciparum infection prevalence and incidence in Southern Province, Zambia.

BACKGROUND: Zambia is pushing for, and has made great strides towards, the elimination of malaria transmission in Southern Province. Reactive focal test and treat (RFTAT) using rapid diagnostic tests and artemether-lumefantrine (AL) has been key in making this progress. Reactive focal drug administration (RFDA) using dihydroartemisinin-piperaquine (DHAP), may be superior in accelerating clearance of the parasite reservoir in humans due to the provision of enhanced chemoprophylactic protection of at-risk populations against new infections. The primary aim of this study is to quantify the relative effectiveness of RFDA with DHAP against RFTAT with AL (standard of care) for reducing Plasmodium falciparum prevalence and incidence. METHODS/DESIGN: The study will be conducted in four districts in Southern Province, Zambia; an area of low malaria transmission and high coverage of vector control. A community randomized controlled trial of 16 health facility catchment areas will be used to evaluate the impact of sustained year-round routine RFDA for 2 years, relative to a control of year-round routine RFTAT. Reactive case detection will be triggered by a confirmed malaria case, e.g., by microscopy or rapid diagnostic test at any government health facility. Reactive responses will be performed by community health workers (CHW) within 7 days of the index case confirmation date. Responses will be performed out to a radius of 140 m from the index case household. A subset of responses will be followed longitudinally for 90 days to examine reinfection rates. Primary outcomes include a post-intervention survey of malaria seropositivity (n = 4800 children aged 1 month to under 5 years old) and a difference-in-differences analysis of malaria parasite incidence, as measured through routine passive case detection at health facilities enrolled in the study. The study is powered to detect approximately a 65% relative reduction in these outcomes between the intervention versus the control. DISCUSSION: Strengths of this trial include a robust study design and an endline cross-sectional parasite survey as well as a longitudinal sample. Primary limitations include statistical power to detect only a 65% reduction in primary outcomes, and the potential for contamination to dilute the effects of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02654912 . Registered on 12 November 2015.

Short-term Impact of Mass Drug Administration With Dihydroartemisinin Plus Piperaquine on Malaria in Southern Province Zambia: A Cluster-Randomized Controlled Trial.

BACKGROUND: Mass drug administration (MDA) using dihydroartemisinin plus piperaquine (DHAp) represents a potential strategy to clear Plasmodium falciparum infections and reduce the human parasite reservoir. METHODS: A cluster-randomized controlled trial in Southern Province, Zambia, was used to assess the short-term impact of 2 rounds of community-wide MDA and household-level (focal) MDA with DHAp compared with no mass treatment. Study end points included parasite prevalence in children, infection incidence, and confirmed malaria case incidence. RESULTS: All end points significantly decreased after intervention, irrespective of treatment group. Parasite prevalence from 7.71% at baseline to 0.54% after MDA in lower-transmission areas, resulting in an 87% reduction compared with control (adjusted odds ratio, 0.13; 95% confidence interval, .02-.92; P = .04). No difference between treatment groups was observed in areas of high transmission. The 5-month cumulative infection incidence was 70% lower (crude incidence rate ratio, 0.30; 95% confidence interval, .06-1.49; P = .14) and 58% lower (0.42; .18-.98; P = .046) after MDA compared with control in lower- and higher-transmission areas, respectively. No significant impact of focal MDA was observed for any end point. CONCLUSIONS: Two rounds of MDA with DHAp rapidly reduced infection prevalence, infection incidence, and confirmed case incidence rates, especially in low-transmission areas. CLINICAL TRIALS REGISTRATION: NCT02329301.

Assessing the effectiveness of household-level focal mass drug administration and community-wide mass drug administration for reducing malaria parasite infection prevalence and incidence in Southern Province, Zambia: study protocol for a community randomized controlled trial.

BACKGROUND: Mass drug administration (MDA) and focal MDA (fMDA) using dihydroartemisinin plus piperaquine (DHAp), represent two strategies to maximize the use of existing information to achieve greater clearance of human infection and reduce the parasite reservoir, and provide longer chemoprophylactic protection against new infections. The primary aim of this study is to quantify the relative effectiveness of MDA and fMDA with DHAp against no mass treatment (standard of care) for reducing Plasmodium falciparum prevalence and incidence. METHODS/DESIGN: The study will be conducted along Lake Kariba in Southern Province, Zambia; an area of low to moderate malaria transmission and high coverage of vector control. A community randomized controlled trial (CRCT) of 60 health facility catchment areas (HFCAs) will be used to evaluate the impact of two rounds of MDA and fMDA interventions, relative to a control of no mass treatment, stratified by high and low transmission. Community residents in MDA HFCAs will be treated with DHAp at the end of the dry season (round one: November to December 2014) and the beginning of the rainy season (round two: February to March 2015). Community residents in fMDA HFCAs will be tested during the same two rounds for malaria parasites with a rapid diagnostic test; all positive individuals and all individuals living in their household will be treated with DHAp. Primary outcomes include malaria parasite prevalence (n = 5,640 children aged one month to under five-years-old), as measured by pre- and post-surveys, and malaria parasite infection incidence (n = 2,250 person-years among individuals aged three months and older), as measured by a monthly longitudinal cohort. The study is powered to detect approximately a 50 % relative reduction in these outcomes between each intervention group versus the control. DISCUSSION: Strengths of this trial include: a robust study design (CRCT); cross-sectional parasite surveys as well as a longitudinal cohort; and stratification of high and low transmission areas. Primary limitations include: statistical power to detect only a 50 % reduction in primary outcomes within high and low transmission strata; potential for contamination; and potential for misclassification of exposure. TRIAL REGISTRATION: Identifier: Clinicaltrials.gov: NCT02329301 . Registration date: 30 December 2014.

Evaluation of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy: a retrospective birth outcomes study in Mansa, Zambia.

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) decreases placental parasitaemia, thus improving birth outcomes. Zambian policy recommends monthly SP-IPTp doses given presumptively during pregnancy at each antenatal examination, spaced one month apart after 16 weeks of gestation. The effectiveness of SP-IPTp was evaluated in Zambia where a recent study showed moderate prevalence of Plasmodium falciparum parasites with genetic mutations that confer SP resistance. METHODS: HIV-negative women were enrolled at the time of delivery at two facilities in Mansa, Zambia, an area of high malaria transmission. Women were interviewed and SP exposure was determined by antenatal card documentation or self-reports. Using Poisson regression modelling, the effectiveness of SP-IPTp was evaluated for outcomes of parasitaemia (microscopic examination of maternal peripheral, cord, and placental blood films), maternal anaemia (Hb < 11 g/dl), placental infection (histopathology), and infant outcomes (low birth weight (LBW), preterm delivery, and small for gestational age) in women who took 0-4 doses of SP-IPTp. RESULTS: Participants included 435 women, with a median age of 23 years (range 16-44). Thirty-four women took zero doses of SP-IPTp, while 115, 142 and 144 women took one, two, or ≥ three doses, respectively. Multivariate Poisson regression models considering age, mosquito net usage, indoor residual spraying, urban home, gravidity, facility, wet season delivery, and marital status showed that among paucigravid women ≥ two doses of SP-ITPp compared to one or less doses was associated with a protective effect on LBW (prevalence ratio (PR) 0.33, 95% confidence interval (CI) 0.12-0.91) and any infection (PR 0.76, CI 0.58-0.99). Multivariate models considering SP-IPTp as a continuous variable showed a protective dose-response association with LBW (paucigravid women: PR 0.54, CI 0.33-0.90, multigravid women: PR 0.63, CI 0.41-0.97). CONCLUSIONS: In Mansa, Zambia, an area of moderate SP resistance, ≥ two doses of SP-IPTp were associated with a protective effect from malaria in pregnancy, especially among paucigravid women. Each dose of SP-IPTp contributed to a 46 and 37% decrease in the frequency of LBW among paucigravid and multigravid women, respectively. SP-IPTp remains a viable strategy in this context.

Therapeutic efficacy of artemether-lumefantrine on treatment of uncomplicated Plasmodium falciparum mono-infection in an area of high malaria transmission in Zambia.

BACKGROUND: Anti-malarial drug resistance continues to be a leading threat to ongoing malaria control efforts and calls for continued monitoring of the efficacy of these drugs in order to inform national anti-malarial drug policy decision-making. This study assessed the therapeutic efficacy and safety of artemether-lumefantrine (AL)(Coartem®) for the treatment of uncomplicated Plasmodium falciparum malaria in two sentinel high malaria transmission districts in the Eastern Province of Zambia in persons aged six months and above, excluding women aged 12 to 18 years. METHODS: This was an observational cohort of 176 symptomatic patients diagnosed with uncomplicated Plasmodium falciparum mono-infection. A World Health Organization (WHO)-standardized 28-day assessment protocol was used to assess clinical and parasitological responses to directly observed AL treatment of uncomplicated malaria. DNA polymerase chain reaction (PCR) analysis for molecular markers of AL resistance was conducted on positive blood samples and differentiated recrudescence from re-infections of the malaria parasites. RESULTS: All patients (CI 97.6-100) had adequate clinical and parasitological responses to treatment with AL. At the time of enrolment, mean slide positivity among study participants was 71.8% and 55.2% in Katete and Chipata, respectively. From a mean parasite density of 55,087, 98% of the study participants presented with zero parasitaemia by day 3 of the study. Fever clearance occurred within 24 hours of treatment with AL. However mean parasite density declines were most dramatic in participants in the older age. No adverse reactions to AL treatment were observed during the study. CONCLUSION: AL remains a safe and efficacious drug for the treatment of uncomplicated Plasmodium falciparum malaria in Zambia, endemic for malaria, with some provinces experiencing high transmission intensity. However, the delayed parasite clearance in younger patients calls for further sentinel and periodical monitoring of AL efficacy in different areas of the country.

Efficacy of sulphadoxine-pyrimethamine for intermittent preventive treatment of malaria in pregnancy, Mansa, Zambia.

BACKGROUND: Intermittent preventive treatment of malaria in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) decreases adverse effects of malaria during pregnancy. Zambia implemented its IPTp-SP programme in 2003. Emergence of SP-resistant Plasmodium falciparum threatens this strategy. The quintuple mutant haplotype (substitutions in N51I, C59R, S108N in dhfr and A437G and K540E in dhps genes), is associated with SP treatment failure in non-pregnant patients with malaria. This study examined efficacy of IPTp-SP and presence of the quintuple mutant among pregnant women in Mansa, Zambia. METHODS: In Mansa, an area with high malaria transmission, HIV-negative pregnant women presenting to two antenatal clinics for the 1st dose of IPTp-SP with asymptomatic parasitaemia were enrolled and microscopy for parasitaemia was done weekly for five weeks. Outcomes were parasitological failure and adequate parasitological response (no parasitaemia during follow-up). Polymerase chain reaction assays were employed to distinguish recrudescence from reinfection, and identify molecular markers of SP resistance. Survival analysis included those who had reinfection and incomplete follow-up (missed at least one follow-up). RESULTS: Of the 109 women included in the study, 58 (53%) completed all follow-up, 34 (31%) had incomplete follow-up, and 17 (16%) were lost to follow-up after day 0. Of those who had complete follow-up, 15 (26%, 95% confidence interval [CI] [16-38]) had parasitological failure. For the 92 women included in the survival analysis, median age was 20 years (interquartile range [IQR] 18-22), median gestational age was 22 weeks (IQR range 20-24), and 57% were primigravid. There was no difference in time to failure in primigravid versus multigravid women. Of the 84 women with complete haplotype data for the aforementioned loci of the dhfr and dhps genes, 53 (63%, 95% CI [50-70]) had quintuple mutants (two with an additional mutation in A581G of dhps). Among women with complete follow-up and quintuple mutants, 22% had parasitological failure versus 0% without (p = 0.44). CONCLUSIONS: While underpowered, this study found 26% failure rates of SP given the moderate prevalence of the quintuple mutant haplotype. Despite the presence of resistance, SP retained some efficacy in clearing parasites in pregnant women, and may remain a viable option for IPTp in Zambia.

Malaria epidemiology and control in Southern Africa.

The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa, following the scale-up of interventions supported by the Roll Back Malaria Partnership, the President's Malaria Initiative and other partners. It is important to appreciate that the reductions in malaria have not been uniform between and within countries, with some areas experiencing resurgence instead. Furthermore, while interventions have greatly reduced the burden of malaria in many countries, it is also recognized that the malaria decline pre-dated widespread intervention efforts, at least in some cases where data are available. This raises more questions as what other factors may have been contributing to the reduction in malaria transmission and to what extent. The International Center of Excellence for Malaria Research (ICEMR) in Southern Africa aims to better understand the underlying malaria epidemiology, vector ecology and parasite genomics using three contrasting settings of malaria transmission in Zambia and Zimbabwe: an area of successful malaria control, an area of resurgent malaria and an area where interventions have not been effective. The Southern Africa ICEMR will capitalize on the opportunity to investigate the complexities of malaria transmission while adapting to intervention and establish the evidence-base to guide effective and sustainable malaria intervention strategies. Key approaches to attain this goal for the region will include close collaboration with national malaria control programs and contribution to capacity building at the individual, institutional and national levels.

Community case management of malaria using ACT and RDT in two districts in Zambia: achieving high adherence to test results using community health workers.

BACKGROUND: Access to prompt and effective treatment is a cornerstone of the current malaria control strategy. Delays in starting appropriate treatment is a major contributor to malaria mortality. WHO recommends home management of malaria using artemisininbased combination therapy (ACT) and Rapid Diagnostic tests (RDTs) as one of the strategies for improving access to prompt and efective malaria case management. METHODS: A prospective evaluation of the effectiveness of using community health workers (CHWs) as delivery points for ACT and RDTs in the home management of malaria in two districts in Zambia. RESULTS: CHWs were able to manage malaria fevers by correctly interpreting RDT results and appropriately prescribing antimalarials. All severe malaria cases and febrile non-malaria fevers were referred to a health facility for further management. There were variations in malaria prevalence between the two districts and among the villages in each district. 100% and 99.4% of the patients with a negative RDT result were not prescribed an antimalarial in the two districts respectively. No cases progressed to severe malaria and no deaths were recorded during the study period. Community perceptions were positive. CONCLUSION: CHWs are effective delivery points for prompt and effective malaria case management at community level. Adherence to test results is the best ever reported in Zambia. Further areas of implementation research are discussed.

Relative costs and effectiveness of treating uncomplicated malaria in two rural districts in Zambia: implications for nationwide scale-up of home-based management.

BACKGROUND: Malaria case management is one of the key strategies to control malaria. Various studies have demonstrated the feasibility of home management of malaria (HMM). However, data on the costs and effectiveness of artemisinin-based combination therapy (ACT) and rapid diagnostic tests via HMM is limited. METHOD: Cost-effectiveness of home management versus health facility-based management of uncomplicated malaria in two rural districts in Zambia was analysed from a providers' perspective. The sample included 16 community health workers (CHWs) and 15 health facilities. The outcome measure was the cost per case appropriately diagnosed and treated. Costs of scaling-up HMM nationwide were estimated based on the CHW utilisation rates observed in the study. RESULTS: HMM was more cost effective than facility-based management of uncomplicated malaria. The cost per case correctly diagnosed and treated was USD 4.22 for HMM and USD 6.12 for facility level. Utilization and adherence to diagnostic and treatment guidelines was higher in HMM than at a health facility. CONCLUSION: HMM using ACT and RDTs was more efficient at appropriately diagnosing and treating malaria than the health facility level. Scaling up this intervention requires significant investments.

Identification of amino acid substitutions associated with neutralization phenotype in the human immunodeficiency virus type-1 subtype C gp120.

Neutralizing antibodies (Nabs) are thought to play an important role in prevention and control of HIV-1 infection and should be targeted by an AIDS vaccine. It is critical to understand how HIV-1 induces Nabs by analyzing viral sequences in both tested viruses and sera. Neutralization susceptibility to antibodies in autologous and heterologous plasma was determined for multiple Envs (3-6) from each of 15 subtype-C-infected individuals. Heterologous neutralization was divided into two distinct groups: plasma with strong, cross-reactive neutralization (n=9) and plasma with weak neutralization (n=6). Plasma with cross-reactive heterologous Nabs also more potently neutralized contemporaneous autologous viruses. Analysis of Env sequences in plasma from both groups revealed a three-amino-acid substitution pattern in the V4 region that was associated with greater neutralization potency and breadth. Identification of such potential neutralization signatures may have important implications for the development of HIV-1 vaccines capable of inducing Nabs to subtype C HIV-1.

Increased risk for severe malaria in HIV-1-infected adults, Zambia.

To determine whether HIV-1 infection and HIV-1-related immunosuppression were risk factors for severe malaria in adults with some immunity to malaria, we conducted a case-control study in Luanshya, Zambia, during December 2005-March 2007. For each case-patient with severe malaria, we selected 2 matched controls (an adult with uncomplicated malaria and an adult without signs of disease). HIV-1 infection was present in 93% of case-patients, in 52% of controls with uncomplicated malaria, and in 45% of asymptomatic controls. HIV-1 infection was a highly significant risk factor for adults with severe malaria compared with controls with uncomplicated malaria (odds ratio [OR] 12.6, 95% confidence interval [CI] 2.0-78.8, p = 0.0005) and asymptomatic controls (OR 16.6, 95% CI 2.5-111.5, p = 0.0005). Persons with severe malaria were more likely to have a CD4 count <350/microL than were asymptomatic controls (OR 23.0, 95% CI 3.35-158.00, p<0.0001).

Early results of integrated malaria control and implications for the management of fever in under-five children at a peripheral health facility: a case study of Chongwe rural health centre in Zambia.

BACKGROUND: Zambia has taken lead in implementing integrated malaria control so as to attain the National Health Strategic Plan goal of "reducing malaria incidence by 75% and under-five mortality due to malaria by 20% by the year 2010". The strategic interventions include the use of long-lasting insecticide-treated nets and indoor residual spraying, the use of artemisinin-based combination therapies (ACT) for the treatment of uncomplicated malaria, improving diagnostic capacity (both microscopy and rapid diagnostic tests), use of intermittent presumptive treatment for pregnant women, research, monitoring and evaluation, and behaviour change communication. Financial barriers to access have been removed by providing free malaria prevention and treatment services. METHODS: Data involving all under-five children reporting at the health facility in the first quarter of 2008 was evaluated prospectively. Malaria morbidity, causes of non-malaria fever, prescription patterns treatment patterns and referral cases were evaluated RESULTS: Malaria infection was found only in 0.7% (10/1378), 1.8% (251378) received anti-malarial treatment, no severe malaria cases and deaths occurred among the under-five children with fever during the three months of the study in the high malaria transmission season. 42.5% (586/1378) of the cases were acute respiratory infections (non-pneumonia), while 5.7% (79/1378) were pneumonia. Amoxicillin was the most prescribed antibiotic followed by septrin. CONCLUSION: Malaria related OPD visits have reduced at Chongwe rural health facility. The reduction in health facility malaria cases has led to an increase in diagnoses of respiratory infections. These findings have implications for the management of non-malaria fevers in children under the age of five years.

Impact of HIV-1 infection on the hematological recovery after clinical malaria.

BACKGROUND: Anemia is the most frequent cytopenia in HIV-infected individuals and is often associated with malaria. OBJECTIVE: To assess the impact of HIV-1 on the hematological recovery after a clinical malaria episode. METHODS: In Ndola, Zambia, a region with high malaria and HIV prevalence, hemoglobin (Hb) was measured in 634 malaria patients 14 and 45 days after antimalarial treatment. Risk factors for hematological recovery were analyzed in a multivariate linear regression model. RESULTS: At enrollment, HIV-1-infected malaria patients had lower Hb compared with HIV-1 uninfected (122.7 vs 136.0 g/L; P < 0.001). In both groups, mean Hb was significantly lower at day 14 posttreatment than day 0 (P < 0.0001) and significantly higher at day 45 than at day 14 (HIV-1 negative: P = 0.0001; HIV-1 infected: P = 0.005). HIV-1 was a risk factor for a larger Hb decrease until day 14 (P < 0.001) and slower recovery until day 45 (P = 0.048). When considering the whole 45-day follow-up period, mean Hb increased in the HIV-1-negative group (+3.54 g/L; 95% confidence interval: 1.37 to 5.70; P = 0.001) but not in the HIV-1-infected group (-0.72 g/L; 95% confidence interval: -3.85 to +2.40; P = 0.64). HIV-1 infection as such (P < 0.0001), not CD4 cell count (P = 0.46), was an independent risk factor for a slower hematological recovery. CONCLUSIONS: HIV-1-infected malaria patients had a slower hematological recovery after successful parasite clearance. Malaria preventive measures should be targeted to this high-risk group.