Publications by authors named "Prudence Hamade"

21 Publications

  • Page 1 of 1

Current malaria infection, previous malaria exposure, and clinical profiles and outcomes of COVID-19 in a setting of high malaria transmission: an exploratory cohort study in Uganda.

Lancet Microbe 2022 Jan 25;3(1):e62-e71. Epub 2021 Oct 25.

Global Technical Team, Malaria Consortium, London, UK.

Background: The potential effects of SARS-CoV-2 and co-infection on host susceptibility and pathogenesis remain unknown. We aimed to establish the prevalence of malaria and describe the clinical characteristics of SARS-CoV-2 and co-infection in a high-burden malaria setting.

Methods: This was an exploratory prospective, cohort study of patients with COVID-19 who were admitted to hospital in Uganda. Patients of all ages with a PCR-confirmed diagnosis of SARS-CoV-2 infection who had provided informed consent or assent were consecutively enrolled from treatment centres in eight hospitals across the country and followed up until discharge or death. Clinical assessments and blood sampling were done at admission for all patients. Malaria diagnosis in all patients was done by rapid diagnostic tests, microscopy, and molecular methods. Previous exposure was determined with serological responses to a panel of antigens assessed using a multiplex bead assay. Additional evaluations included complete blood count, markers of inflammation, and serum biochemistries. The main outcome was overall prevalence of malaria infection and malaria prevalence by age (including age categories of 0-20 years, 21-40 years, 41-60 years, and >60 years). The frequency of symptoms was compared between patients with COVID-19 with infection versus those without infection. The frequency of comorbidities and COVID-19 clinical severity and outcomes was compared between patients with low previous exposure to versus those with high previous exposure to . The effect of previous exposure to on COVID-19 clinical severity and outcomes was also assessed among patients with and those without comorbidities.

Findings: Of 600 people with PCR-confirmed SARS-CoV-2 infection enrolled from April 15, to Oct 30, 2020, 597 (>99%) had complete information and were included in our analyses. The majority (502 [84%] of 597) were male individuals with a median age of 36 years (IQR 28-47). Overall prevalence of infection was 12% (95% CI 9·4-14·6; 70 of 597 participants), with highest prevalence in the age groups of 0-20 years (22%, 8·7-44·8; five of 23 patients) and older than 60 years (20%, 10·2-34·1; nine of 46 patients). Confusion (four [6%] of 70 patients eight [2%] of 527 patients; p=0·040) and vomiting (four [6%] of 70 patients five [1%] of 527 patients; p=0·014] were more frequent among patients with infection than those without. Patients with low versus those with high previous exposure had a increased frequency of severe or critical COVID-19 clinical presentation (16 [30%] of 53 patients three [5%] of 56 patients; p=0·0010) and a higher burden of comorbidities, including diabetes (12 [23%] of 53 patients two [4%] of 56 patients; p=0·0010) and heart disease (seven [13%] of 53 patients zero [0%] of 56 patients; p=0·0030). Among patients with no comorbidities, those with low previous exposure still had a higher proportion of cases of severe or critical COVID-19 than did those with high exposure (six [18%] of 33 patients one [2%] of 49 patients; p=0·015). Multivariate analysis showed higher odds of unfavourable outcomes in patients who were older than 60 years (adjusted OR 8·7, 95% CI 1·0-75·5; p=0·049).

Interpretation: Although patients with COVID-19 with co-infection had a higher frequency of confusion and vomiting, co-infection did not seem deleterious. The association between low previous malaria exposure and severe or critical COVID-19 and other adverse outcomes will require further study. These preliminary descriptive observations highlight the importance of understanding the potential clinical and therapeutic implications of overlapping co-infections.

Funding: Malaria Consortium (USA).
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http://dx.doi.org/10.1016/S2666-5247(21)00240-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8545833PMC
January 2022

A feasibility study to assess non-clinical community health workers' capacity to use simplified protocols and tools to treat severe acute malnutrition in Niger state Nigeria.

BMC Health Serv Res 2021 Oct 15;21(1):1102. Epub 2021 Oct 15.

Malaria Consortium, London, UK.

Background: Severe acute malnutrition (SAM) is a major determinant of childhood mortality and morbidity. Although integrated community case management (iCCM) of childhood illnesses is a strategy for increasing access to life-saving treatment, malnutrition is not properly addressed in the guidelines. This study aimed to determine whether non-clinical Community Health Workers (called Community-Oriented Resource Persons, CORPs) implementing iCCM could use simplified tools to treat uncomplicated SAM.

Methods: The study used a sequential multi-method design and was conducted between July 2017 and May 2018. Sixty CORPs already providing iCCM services were trained and deployed in their communities with the target of enrolling 290 SAM cases. Competency of CORPs to treat and the treatment outcomes of enrolled children were documented. SAM cases with MUAC of 9 cm to < 11.5 cm without medical complications were treated for up to 12 weeks. Full recovery was at MUAC≥12.5 cm for two consecutive weeks. Supervision and quantitative data capturing were done weekly while qualitative data were collected after the intervention.

Results: CORPs scored 93.1% on first assessment and increment of 0.11 (95% CI, 0.05-0.18) points per additional supervision conducted. The cure rate from SAM to full recovery, excluding referrals from the denominator in line with the standard for reporting SAM recovery rates, was 73.5% and the median length of treatment was 7 weeks. SAM cases enrolled at 9 cm to < 10.25 cm MUAC had 31% less likelihood of recovery compared to those enrolled at 10.25 cm to < 11.5 cm. CORPs were not burdened by the integration of SAM into iCCM and felt motivated by children's recovery. Operational challenges like bad terrains for supervision, supply chain management and referrals were reported by supervisors, while Government funding was identified as key for sustainability.

Conclusion: The study demonstrated that with training and supportive supervision, CORPs in Nigeria can treat SAM among under-fives, and refer complicated cases using simplified protocols as part of an iCCM programme. This approach seemed acceptable to all stakeholders, however, the effect of the extra workload of integrating SAM into iCCM on the quality of care provided by the CORPs should be assessed further.
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http://dx.doi.org/10.1186/s12913-021-07118-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8520247PMC
October 2021

Prevalence and seroprevalence of Plasmodium infection in Myanmar reveals highly heterogeneous transmission and a large hidden reservoir of infection.

PLoS One 2021 9;16(6):e0252957. Epub 2021 Jun 9.

Ministry of Health and Sports, Yangon, Myanmar.

Malaria incidence in Myanmar has significantly reduced over recent years, however, completeness and timeliness of incidence data remain a challenge. The first ever nationwide malaria infection and seroprevalence survey was conducted in Myanmar in 2015 to better understand malaria epidemiology and highlight gaps in Annual Parasite Index (API) data. The survey was a cross-sectional two-stage stratified cluster-randomised household survey conducted from July-October 2015. Blood samples were collected from household members for ultra-sensitive PCR and serology testing for P. falciparum and P. vivax. Data was gathered on demography and a priori risk factors of participants. Data was analysed nationally and within each of four domains defined by API data. Prevalence and seroprevalence of malaria were 0.74% and 16.01% nationwide, respectively. Prevalent infection was primarily asymptomatic P. vivax, while P. falciparum was predominant in serology. There was large heterogeneity between villages and by domain. At the township level, API showed moderate correlation with P. falciparum seroprevalence. Risk factors for infection included socioeconomic status, domain, and household ownership of nets. Three K13 P. falciparum mutants were found in highly prevalent villages. There results highlight high heterogeneity of both P. falciparum and P. vivax transmission between villages, accentuated by a large hidden reservoir of asymptomatic P. vivax infection not captured by incidence data, and representing challenges for malaria elimination. Village-level surveillance and stratification to guide interventions to suit local context and targeting of transmission foci with evidence of drug resistance would aid elimination efforts.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252957PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189444PMC
November 2021

The impact of malaria coinfection on Ebola virus disease outcomes: A systematic review and meta-analysis.

PLoS One 2021 24;16(5):e0251101. Epub 2021 May 24.

Malaria Consortium, London, United Kingdom.

Introduction: Viral outbreaks present a particular challenge in countries in Africa where there is already a high incidence of other infectious diseases, including malaria which can alter immune responses to secondary infection. Ebola virus disease (EVD) is one such problem; understanding how Plasmodium spp. and Ebolavirus (EBOV) interact is important for future outbreaks.

Methods: We conducted a systematic review in PubMed and Web of Science to find peer-reviewed papers with primary data literature to determine 1) prevalence of EBOV/Plasmodium spp. coinfection, 2) effect of EBOV/Plasmodium spp. coinfection on EVD pathology and the immune response, 3) impact of EBOV/Plasmodium spp. coinfection on the outcome of EVD-related mortality. Random effects meta-analyses were conducted with the R package meta to produce overall proportion and effect estimates as well as measure between-study heterogeneity.

Results: From 322 peer-reviewed papers, 17 were included in the qualitative review and nine were included in a meta-analysis. Prevalence of coinfection was between 19% and 72%. One study reported significantly lower coagulatory response biomarkers in coinfected cases but no difference in inflammatory markers. Case fatality rates were similar between EBOV(+)/Pl(+) and EBOV(+)/Pl(-) cases (62.8%, 95% CI 49.3-74.6 and 56.7%, 95% CI 53.2-60.1, respectively), and there was no significant difference in risk of mortality (RR 1.09, 95% CI 0.90-1.31) although heterogeneity between studies was high. One in vivo mouse model laboratory study found no difference in mortality by infection status, but another found prior acute Plasmodium yoeli infection was protective against morbidity and mortality via the IFN-γ signalling pathway.

Conclusion: The literature was inconclusive; studies varied widely and there was little attempt to adjust for confounding variables. Laboratory studies may present the best option to answer how pathogens interact within the body but improvement in data collection and analysis and in diagnostic methods would aid patient studies in the future.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251101PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143409PMC
October 2021

Navigating the COVID-19 Crisis to Sustain Community-Based Malaria Interventions in Cambodia.

Glob Health Sci Pract 2021 06 30;9(2):344-354. Epub 2021 Jun 30.

Provincial Health Department, Preah Vihear Province, Ministry of Health of Cambodia, Preah Vihear, Cambodia.

Cambodia has made impressive progress in reducing malaria trends and, in 2018, reported no malaria-related deaths for the first time. However, the coronavirus disease (COVID-19) pandemic presents a potential challenge to the country's goal for malaria elimination by 2025. The path toward malaria elimination depends on sustained interventions to prevent rapid resurgence, which can quickly set back any gains achieved.Malaria Consortium supported mobile malaria workers (MMWs) to engage with target communities to build acceptance, trust, and resilience. At the start of the pandemic, Malaria Consortium conducted a COVID-19 risk assessment and quickly developed and implemented a mitigation plan to ensure MMWs were able to continue providing malaria services without putting themselves or their patients at risk. Changes in malaria intervention coverage and community uptake have been monitored to gauge the indirect effects of COVID-19. Comparisons have been made between output indicators reported in 2020 and from the same month-period of the previous year.In general, malaria service intervention coverage and utilization rates did not decline in 2020. Rather, the reported figures show there was a substantial increase in service utilization. Preliminary internal reviews and community meetings show that despite a heightened public risk perception toward COVID-19, malaria testing motivation has been well sustained throughout the pandemic. This may be attributable to proactive program planning and data monitoring and active engagement with the communities and the national authorities to circumvent the indirect effect of COVID-19 on intervention coverage in Cambodia during the pandemic.
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http://dx.doi.org/10.9745/GHSP-D-20-00528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324197PMC
June 2021

Antibiotic practices among household members and their domestic animals within rural communities in Cumilla district, Bangladesh: a cross-sectional survey.

BMC Public Health 2021 02 25;21(1):406. Epub 2021 Feb 25.

Nuffield Centre for International Health and Development, University of Leeds, Leeds, LS2 9JT, UK.

Background: Antibiotic resistance is a global threat to human health, and inappropriate use of antibiotics in humans and animals is widely considered to be a key driver of antibiotic resistant infections. Antibiotic use in humans and animals is growing rapidly in low- and, particularly, middle-income countries. However, there is little detailed understanding about practices related to the use of antibiotics in humans and animals within community settings in such countries. Here we aimed to understand the antibiotic practices of rural households across Cumilla district, Bangladesh, in relation to household members and their domestic animals.

Methods: In 2018 we conducted a cross-sectional survey using representative cluster sampling methods. We collected self-reported information from 682 female and 620 male household heads, with women also asked about their children's antibiotic practices.

Results: Only 48% (95% CI: 40, 56%) of women and men had heard of antibiotics, and among those women and men who were aware of antibiotics and the children of those women 70% (95% CI: 64, 76%) reported having previously taken antibiotics, while among these individuals who reported previously taking antibiotics 21% (95% CI: 18, 25%) said they had done so most recently within the last month. Risky/inappropriate antibiotic practices in humans and animals were often reported. For example, among women and men who were aware of antibiotics and the children of those women 52% (95% CI: 40, 63%) reported previously taking antibiotics for a "cough/cold", despite antibiotics being typically inappropriate for use against viral upper respiratory tract infections. Among poultry-owning respondents who were aware of antibiotics 11% (95% CI: 8, 15%) reported previously giving healthy poultry antibiotics, mainly for growth/prophylaxis, while among cattle-owning respondents who were aware of antibiotics and reported previously giving their cattle feed 20% (95% CI: 9, 37%) said the feed had contained antibiotics at least sometimes.

Conclusions: Our results highlight the need for context-adapted interventions at both the community level and the health systems level to reduce inappropriate antibiotic use among humans and domestic animals in rural Bangladesh. Successfully reducing inappropriate use of antibiotics among humans and animals is a required and critical step in tackling antimicrobial resistance.
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http://dx.doi.org/10.1186/s12889-021-10457-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908663PMC
February 2021

Eliminating Plasmodium falciparum malaria: results from tailoring active case detection approaches to remote populations in forested border areas in north-eastern Cambodia.

Malar J 2021 Feb 22;20(1):108. Epub 2021 Feb 22.

Malaria Consortium, Phnom Penh, Cambodia.

Background: Remaining Plasmodium falciparum cases in Cambodia are concentrated in forested border areas and in remote populations who are hard to reach through passive case detection. A key approach to reach these populations is active case detection by mobile malaria workers (MMWs). However, this is operationally challenging because of changing movement patterns of the target population moving into less accessible areas. From January 2018 to December 2020, a tailored package of active case detection approaches was implemented in forested border areas of three provinces in north-eastern Cambodia to reach remote populations and support the elimination of falciparum malaria.

Methods: Key elements of this project were to tailor approaches to local populations, use responsive monitoring systems, maintain operational flexibility, build strong relationships with local communities, and implement close supervision practices. MMWs were recruited from local communities. Proactive case detection approaches included mobile malaria posts positioned at frequented locations around and within forests, and locally informed outreach activities targeting more remote locations. Reactive case detection was conducted among co-travellers of confirmed cases. Testing for malaria was conducted independent of fever symptoms. Routine monitoring of programmatic data informed tactical adaptations, while supervision exercises ensured service quality.

Results: Despite operational challenges, service delivery sites were able to maintain consistently high testing rates throughout the implementation period, with each of 45 sites testing a monthly average of 64 (SD 6) people in 2020. In 2020, project MMWs detected only 32 P. falciparum cases. Over the project period, the P. falciparum/P. vivax ratio steadily inversed. Including data from neighbouring health centres and village malaria workers, 45% (80,988/180,732) of all people tested and 39% (1280/3243) of P. falciparum cases detected in the area can be attributed to project MMWs. Remaining challenges of the last elimination phase include maintaining intensified elimination efforts, addressing the issue of detecting low parasitaemia cases and shifting focus to P. vivax malaria.

Conclusions: Reaching remote populations through active case detection should remain a key strategy to eliminate P. falciparum malaria. This case study presented a successful approach combining tailored proactive and reactive strategies that could be transferred to similar settings in other areas of the Greater Mekong Subregion.
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http://dx.doi.org/10.1186/s12936-021-03622-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898252PMC
February 2021

Health systems readiness and quality of inpatient malaria case-management in Kano State, Nigeria.

Malar J 2020 Oct 30;19(1):384. Epub 2020 Oct 30.

KEMRI-Wellcome Trust Research Programme, Nairobi, Kenya.

Background: Nigeria was among the first African countries to adopt and implement change of treatment policy for severe malaria from quinine to artesunate. Seven years after the policy change health systems readiness and quality of inpatient malaria case-management practices were evaluated in Kano State of Nigeria.

Methods: A cross-sectional survey was undertaken in May 2019 at all public hospitals. Data collection comprised hospital assessments, interviews with inpatient health workers and data extraction from medical files for all suspected malaria patients admitted to the paediatric and medical wards in April 2019. Descriptive analyses included 22 hospitals, 154 health workers and 1,807 suspected malaria admissions analysed from malaria test and treat case-management perspective.

Results: 73% of hospitals provided malaria microscopy, 27% had rapid diagnostic tests and 23% were unable to perform any parasitological malaria diagnosis. Artemisinin-based combination therapy (ACT) was available at 96% of hospitals, artemether vials at 68% while injectable quinine and artesunate were equally stocked at 59% of hospitals. 32%, 21% and 15% of health workers had been exposed to relevant trainings, guidelines and supervision respectively. 47% of suspected malaria patients were tested while repeat testing was rare (7%). 60% of confirmed severe malaria patients were prescribed artesunate. Only 4% of admitted non-severe test positive cases were treated with ACT, while 76% of test negative patients were prescribed an anti-malarial. Artemether was the most common anti-malarial treatment for non-severe test positive (55%), test negative (43%) and patients not tested for malaria (45%). In all categories of the patients, except for confirmed severe cases, artemether was more commonly prescribed for adults compared to children. 44% of artesunate-treated patients were prescribed ACT follow-on treatment. Overall compliance with test and treat policy for malaria was 13%.

Conclusions: Translation of new treatment policy for severe malaria into inpatient practice is compromised by lack of malaria diagnostics, stock-outs of artesunate and suboptimal health workers' practices. Establishment of the effective supply chain and on-going supportive interventions for health workers accompanied with regular monitoring of the systems readiness and clinical practices are urgently needed.
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http://dx.doi.org/10.1186/s12936-020-03449-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602350PMC
October 2020

A process for developing a sustainable and scalable approach to community engagement: community dialogue approach for addressing the drivers of antibiotic resistance in Bangladesh.

BMC Public Health 2020 Jun 17;20(1):950. Epub 2020 Jun 17.

ARK Foundation, Suite C-3 &C-4, House 06, Road 109, Gulshan2, Dhaka, 1212, Bangladesh.

Background: Community engagement approaches that have impacted on health outcomes are often time intensive, small-scale and require high levels of financial and human resources. They can be difficult to sustain and scale-up in low resource settings. Given the reach of health services into communities in low income countries, the health system provides a valuable and potentially sustainable entry point that would allow for scale-up of community engagement interventions. This study explores the process of developing an embedded approach to community engagement taking the global challenge of antibiotic resistance as an example.

Methods: The intervention was developed using a sequential mixed methods study design. This consisted of: exploring the evidence base through an umbrella review, and identifying key international standards on the appropriate use of antibiotics; undertaking detailed formative research through a) a qualitative study to explore the most appropriate mechanisms through which to embed the intervention within the existing health system and community infrastructure, and to understand patterns of knowledge, attitudes and practice regarding antibiotics and antibiotic resistance; and b) a household survey - which drew on the qualitative findings - to quantify knowledge, and reported attitudes and practice regarding antibiotics and antibiotic resistance within the target population; and c) drawing on appropriate theories regarding change mechanisms and experience of implementing community engagement interventions to co-produce the intervention processes and materials with key stakeholders at policy, health system and community level.

Results: A community engagement intervention was co-produced and was explicitly designed to link into existing health system and community structures and be appropriate for the cultural context, and therefore have the potential to be implemented at scale. We anticipate that taking this approach increases local ownership, as well as the likelihood that the intervention will be sustainable and scalable.

Conclusions: This study demonstrates the value of ensuring that a range of stakeholders co-produce the intervention, and ensuring that the intervention is designed to be appropriate for the health system, community and cultural context.
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http://dx.doi.org/10.1186/s12889-020-09033-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7302129PMC
June 2020

Evaluation of a capacity building intervention on malaria treatment for under-fives in rural health facilities in Niger State, Nigeria.

Malar J 2020 Feb 24;19(1):90. Epub 2020 Feb 24.

Disease Control Department, London School of Hygiene & Tropical Medicine, London, WC1E 7HT, UK.

Background: Despite the uptake of parasitological testing into policy and practice, appropriate prescription of anti-malarials and artemisinin-based combination therapy (ACT) in accordance with test results is variable. This study describes a National Malaria Control Programme-led capacity building intervention which was implemented in 10 States of Nigeria. Using the experience of Niger State, this study assessed the effect on malaria diagnosis and prescription practices among febrile under-fives in rural health facilities.

Methods: The multicomponent capacity building intervention consisted of revised case management manuals; cascade training from national to state level carried out at the local government area (LGA) level; and on the job capacity development through supportive supervision. The evaluation was conducted in 28, principally government-owned, health facilities in two rural LGAs of Niger State, one in which the intervention case management of malaria was implemented and the other acted as a comparison area with no implementation of the intervention. Three outcomes were considered in the context of rapid diagnostic testing (RDT) for malaria which were: the prevalence of RDT testing in febrile children; appropriate treatment of RDT-positive children; and appropriate treatment of RDT-negative children. Outcomes were compared post-intervention between intervention and comparison areas using multivariate logistic regression.

Results: The intervention did not improve appropriate management of under-fives in intervention facilities above that seen for under-fives in comparison facilities. Appropriate treatment with artemisinin-based combinations of RDT-positive and RDT-negative under-fives was equally high in both areas. However, appropriate treatment of RDT-negative children, when defined as receipt of no ACT or any other anti-malarials, was better in comparison areas. In both areas, a small number of RDT-positives were not given ACT, but prescribed an alternative anti-malarial, including artesunate monotherapy. Among RDT-negatives, no under-fives were prescribed artesunate as monotherapy.

Conclusion: In a context of significant stock-outs of both ACT medicines and RDTs, under-fives were not more appropriately managed in intervention than comparison areas. The malaria case management intervention implemented through cascade training reached only approximately half of health workers managing febrile under-fives in this setting. Implementation studies on models of cascade training are needed to define what works in what context.
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http://dx.doi.org/10.1186/s12936-020-03167-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041190PMC
February 2020

Gender-related factors affecting health seeking for neglected tropical diseases: findings from a qualitative study in Ethiopia.

PLoS Negl Trop Dis 2019 12 12;13(12):e0007840. Epub 2019 Dec 12.

Malaria Consortium, Addis Ababa, Ethiopia.

Background: Despite known gender-specific differences in terms of prevalence, transmission and exposure to neglected tropical diseases (NTDs), there is limited discussion of the influence of gender in NTD programmes and interventions. There is a paucity of research on how gender interacts with NTD service provision and uptake. This study, part of broader implementation research in Ethiopia, applied a gender lens to health seeking for five NTDs: lymphatic filariasis, podoconiosis, schistosomiasis, soil-transmitted helminth infection and trachoma.

Methodology/principal Findings: The study was conducted in a district of the Southern Nations, Nationalities, and Peoples' Region of Ethiopia where the five NTDs are prevalent. A qualitative methodology was adopted to explore participants' perspectives and experiences. Data generation methods included 20 interviews and four focus group discussions. Community members, volunteer Health Development Army leaders, Health Extension Workers and a range of health workers at the health post, health centre and hospital level (n = 59) were purposively sampled. Interviews and focus group discussions were audio recorded, transcribed verbatim into English then analysed through open coding, drawing on constant comparative methods. Gender related factors affected care seeking for NTDs and were described as reasons for not seeking care, delayed care seeking and treating NTDs with natural remedies. Women faced additional challenges in seeking health care due to gender inequalities and power dynamics in their domestic partnerships. Participants recommended raising community awareness about NTDs, however this remains problematic due to gender and social norms around appropriate discourse with members of the opposite gender.

Conclusions/significance: The findings from this study provide crucial insights into how gender interacts with accessing health services, at different levels of the health system. If we are committed to leaving no one behind and achieving universal health coverage, it is essential to address gender disparities to access and utilisation of interventions delivered by national NTD programmes.
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http://dx.doi.org/10.1371/journal.pntd.0007840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907747PMC
December 2019

Consequences of restricting antimalarial drugs to rapid diagnostic test-positive febrile children in south-west Nigeria.

Trop Med Int Health 2019 11 3;24(11):1291-1300. Epub 2019 Oct 3.

London School of Tropical Medicine and Hygiene, London, UK.

Objectives: To investigate the consequence of restricting antimalarial treatment to febrile children that test positive to a malaria rapid diagnostic test (MRDT) only in an area of intense malaria transmission.

Methods: Febrile children aged 3-59 months were screened with an MRDT at health facilities in south-west Nigeria. MRDT-positive children received artesunate-amodiaquine (ASAQ), while MRDT-negative children were treated based on the clinical diagnosis of non-malaria febrile illness. The primary endpoint was the risk of developing microscopy-positive malaria within 28 days post-treatment.

Results: 309 (60.5%) of 511 children were MRDT-positive while 202 (39.5%) were MRDT-negative at enrolment. 18.5% (50/275) of MRDT-positive children and 7.6% (14/184) of MRDT-negative children developed microscopy-positive malaria by day 28 post-treatment (ρ = 0.001). The risk of developing clinical malaria by day 28 post-treatment was higher among the MRDT-positive group than the MRDT-negative group (adjusted OR 2.74; 95% CI, 1.4, 5.4). A higher proportion of children who were MRDT-positive at enrolment were anaemic on day 28 compared with the MRDT-negative group (12.6% vs. 3.1%; ρ = 0.001). Children in the MRDT-negative group made more unscheduled visits because of febrile illness than those in MRDT-positive group (23.2% vs. 12.0%; ρ = 0.001).

Conclusion: Restricting ACT treatment to MRDT-positive febrile children only did not result in significant adverse outcomes. However, the risk of re-infection within 28 days was significantly higher among MRDT-positive children despite ASAQ treatment. A longer-acting ACT may be needed as the first-line drug of choice for treating uncomplicated malaria in high-transmission settings to prevent frequent re-infections.
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http://dx.doi.org/10.1111/tmi.13304DOI Listing
November 2019

Molecular determinants of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum in Nigeria and the regional emergence of dhps 431V.

Int J Parasitol Drugs Drug Resist 2016 12 29;6(3):220-229. Epub 2016 Sep 29.

Department of Pathogen Molecular Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

There are few published reports of mutations in dihydropteroate synthetase (dhps) and dihydrofolate reductase (dhfr) genes in P. falciparum populations in Nigeria, but one previous study has recorded a novel dhps mutation at codon 431 among infections imported to the United Kingdom from Nigeria. To assess how widespread this mutation is among parasites in different parts of the country and consequently fill the gap in sulfadoxine-pyrimethamine (SP) resistance data in Nigeria, we retrospectively analysed 1000 filter paper blood spots collected in surveys of pregnant women and children with uncomplicated falciparum malaria between 2003 and 2015 from four sites in the south and north. Genomic DNA was extracted from filter paper blood spots and placental impressions. Point mutations at codons 16, 50, 51, 59, 108, 140 and 164 of the dhfr gene and codons 431, 436, 437, 540, 581 and 613 of the dhps gene were evaluated by nested PCR amplification followed by direct sequencing. The distribution of the dhps-431V mutation was widespread throughout Nigeria with the highest prevalence in Enugu (46%). In Ibadan where we had sequential sampling, its prevalence increased from 0% to 6.5% between 2003 and 2008. Although there were various combinations of dhps mutations with 431V, the combination 431V + 436A + 437G+581G+613S was the most common. All these observations support the view that dhps-431V is on the increase. In addition, P. falciparum DHPS crystal structure modelling shows that the change from Isoleucine to Valine (dhps-431V) could alter the effects of both S436A/F and A437G, which closely follow the 2nd β-strand. Consequently, it is now a research priority to assess the implications of dhps-VAGKGS mutant haplotype on continuing use of SP in seasonal malaria chemoprevention (SMC) and intermittent preventive treatment in pregnancy (IPTp). Our data also provides surveillance data for SP resistance markers in Nigeria between 2003 and 2015.
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http://dx.doi.org/10.1016/j.ijpddr.2016.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094156PMC
December 2016

Health worker and policy-maker perspectives on use of intramuscular artesunate for pre-referral and definitive treatment of severe malaria at health posts in Ethiopia.

Malar J 2016 Oct 18;15(1):507. Epub 2016 Oct 18.

Malaria Consortium UK, London, UK.

Background: The World Health Organization (WHO) recommends injectable artesunate given either intravenously or by the intramuscular route for definitive treatment for severe malaria and recommends a single intramuscular dose of intramuscular artesunate or intramuscular artemether or intramuscular quinine, in that order of preference as pre-referral treatment when definitive treatment is not possible. Where intramuscular injections are not available, children under 6 years may be administered a single dose of rectal artesunate. Although the current malaria treatment guidelines in Ethiopia recommend intra-rectal artesunate or alternatively intramuscular artemether or intramuscular quinine as pre-referral treatment for severe malaria at the health posts, there are currently no WHO prequalified suppliers of intra-rectal artesunate and when available, its use is limited to children under 6 years of age leaving a gap for the older age groups. Intramuscular artesunate is not part of the drugs recommended for pre-referral treatment in Ethiopia. This study assessed the perspectives of health workers, and policy-makers on the use of intramuscular artesunate as a pre-referral and definitive treatment for severe malaria at the health post level.

Methods: In-depth interviews were held with 101 individuals including health workers, malaria focal persons, and Regional Health Bureaus from Oromia and southern nations, nationalities, and peoples' region, as well as participants from the Federal Ministry of Health and development partners. An interview guide was used in the data collection and thematic content analysis was employed for analysis.

Results: Key findings from this study are: (1) provision of intramuscular artesunate as pre-referral and definitive treatment for severe malaria at health posts could be lifesaving; (2) with adequate training, and provision of facilities including beds, health posts can provide definitive treatment for severe malaria using intramuscular artesunate where referral is delayed or not possible; (3) health workers at health centres and hospitals frequently use the intravenous route because it allows for co-administration of other drugs, but they find the intramuscular route easier to use at the health post level; (4) the reasons commonly cited against the management of severe malaria using intramuscular artesunate at health post level were: lack of capacity to manage complications and fear of irrational drug use; (5) use of intramuscular artesunate at health post level will require evidence on safety and feasibility before policy shift.

Conclusion: From the perspective of health workers, use of intramuscular artesunate as pre-referral treatment of severe malaria cases at the health post is possible but dependent on training and availability of skilled workers. Use of intramuscular artesunate as definitive treatment at health posts was not supported, however, operational research to establish its feasibility, safety and efficacy was recommended to guide any implementation of such an intervention.
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http://dx.doi.org/10.1186/s12936-016-1561-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070158PMC
October 2016

Health worker perspectives on the possible use of intramuscular artesunate for the treatment of severe malaria at lower-level health facilities in settings with poor access to referral facilities in Nigeria: a qualitative study.

BMC Health Serv Res 2016 10 12;16(1):566. Epub 2016 Oct 12.

Malaria Consortium Africa Region, P.O Box 8045, Kampala, Uganda.

Background: Innovative strategies are needed to reduce malaria mortality in high burden countries like Nigeria. Given that one of the important reasons for this high malaria mortality is delay in receiving effective treatment, improved access to such treatment is critical. Intramuscular artesunate could be used at lower-level facilities given its proven efficacy, ease of use and excellent safety profile. The objective of this study was therefore to explore health workers' perspectives on the possible use of intramuscular artesunate as definitive treatment for severe malaria at lower-level facilities, especially when access to referral facilities is challenging. The study was to provide insight as a formative step into the conduct of future experimental studies to ascertain the feasibility of the use of intramuscular artesunate for definitive treatment of severe malaria in lower level facilities where access to referral care is limited.

Methods: This qualitative study was done across three southern States in Nigeria (Oyo, Cross River and Enugu). Key informant interviews were conducted over a period of three months between October and December 2014 among 90 purposively selected health workers with different roles in malaria case management from primary care to policy level. A thematic content analysis was used to analyse data.

Results: Overall, most of health workers and other key informant groups thought that the use of intramuscular artesunate for definitive treatment of severe malaria at lower-level facilities was possible. They however reported human resource and infrastructure constraints as factors affecting the feasibility of intramuscular artesunate use as definitive treatment for severe malaria in lower-level facilities.. Specifically identified barriers included limited numbers of skilled health workers available to manage potential complications of severe malaria and poorly equipped facilities for supportive treatment. Intramuscular artesunate was considered easy to administer and the proximity of lower-level facilities to communities was deemed important in considering the possibility of its use at lower-level facilities. Health workers also emphasised the important role of operational research to provide additional evidence to guide the implementation of existing policy recommendations and inform future policy revisions.

Conclusions: From the perspective of health workers, use of intramuscular artesunate for definitive treatment of severe malaria at lower-level health facilities in Nigeria is possible but dependent on availability of skilled workers, well-equipped lower-level facilities to provide supportive treatment There is need for further operational research to establish feasibility and guide the implementation of such an intervention.
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http://dx.doi.org/10.1186/s12913-016-1811-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5059903PMC
October 2016

The use of formative research to inform the design of a seasonal malaria chemoprevention intervention in northern Nigeria.

Malar J 2016 09 15;15:474. Epub 2016 Sep 15.

Malaria Consortium, Development House, 56-64 Leonard Street, London, EC2A 4LT, UK.

Background: Experience of seasonal malaria chemoprevention (SMC) is growing in the Sahel sub-region of Africa, though there remains insufficient evidence to recommend a standard deployment strategy. In 2012, a project was initiated in Katsina state, northern Nigeria, to design an appropriate and effective community-based delivery approach for SMC, in consultation with local stakeholders. Formative research (FR) was conducted locally to explore the potential feasibility and acceptability of SMC and to highlight information gaps and practical considerations to inform the intervention design.

Methods: The FR adopted qualitative methods; 36 in-depth interviews and 18 focus group discussions were conducted across 13 target groups active across the health system and within the community. Analysis followed the 'framework' approach. The process for incorporating the FR results into the project design was iterative which was initiated by a week-long 'intervention design' workshop with relevant stakeholders.

Results: The FR highlighted both supportive and hindering factors to be considered in the intervention design. Malaria control was identified as a community priority, the community health workers were a trusted resource and the local leadership exerted strong influence over household decisions. However, there were perceived challenges with quality of care at both community and health facility levels, referral linkage and supportive supervision were weak, literacy levels lower than anticipated and there was the potential for suspicion of 'outside' interventions. There was broad consensus across target groups that community-based SMC drug delivery would better enable a high coverage of beneficiaries and potentially garner wider community support. A mixed approach was recommended, including both community fixed-point and household-to-household SMC delivery. The FR findings were used to inform the overall distribution strategy, mechanisms for integration into the health system, capacity building and training approaches, supportive interventions to strengthen the health system, and the social mobilization strategy.

Conclusions: Formative research played a valuable role in exploring local socio-cultural contexts and health system realities. Both opportunities and challenges for the introduction of SMC delivery were highlighted, which were appropriately considered in the design of the project.
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http://dx.doi.org/10.1186/s12936-016-1526-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025607PMC
September 2016

Rational use of antibiotics by community health workers and caregivers for children with suspected pneumonia in Zambia: a cross-sectional mixed methods study.

BMC Public Health 2016 08 27;16:897. Epub 2016 Aug 27.

Malaria Consortium, Development House, 56-64 Leonard Street, London, EC2A 4LT, UK.

Background: Antibiotic resistance is an issue of growing global concern. One key strategy to minimise further development of resistance is the rational use of antibiotics, by providers and patients alike. Through integrated community case management (iCCM), children diagnosed with suspected pneumonia are treated with antibiotics; one component of an essential package to reduce child mortality and increase access to health care for remote populations. Through the use of clinical algorithms, supportive supervision and training, iCCM also offers the opportunity to improve the rational use of antibiotics and limit the spread of resistance in resource-poor contexts. This study provides evidence on antibiotic use by community health workers (CHWs) and caregivers to inform iCCM programmes, safeguarding current treatments whilst maximising access to care.

Methods: 1497 CHW consultations were directly observed by non-clinical researchers, with measurement of respiratory rate by CHWs recorded by video. Videos were used to conduct a retrospective reference standard assessment of respiratory rate by experts. Fifty-five caregivers whose children were prescribed a 5-day course of antibiotics for suspected pneumonia were followed up on day six to assess adherence through structured interviews and pill counts. Six focus group discussions and nine in depth interviews were conducted with CHWs and caregivers to supplement quantitative findings.

Results: The findings indicate that CHWs adhered to treatment guidelines for 92 % of children seen, prescribing treatment corresponding to their assessment. However, only 65 % of antibiotics prescribed were given for children with experts' confirmed fast breathing pneumonia. Qualitative data indicates that CHWs have a good understanding of pneumonia diagnosis, and although caregivers sometimes applied pressure to receive drugs, CHWs stated that treatment decisions were not influenced. 46 % of caregivers were fully adherent and gave their child the full 5-day course of dispersible amoxicillin. If caregivers who gave treatment for 3 to 5 days were considered, adherence increased to 76 %.

Conclusions: CHWs are capable of prescribing treatment corresponding to their assessment of respiratory rate. However, rational use of antibiotics could be strengthened through improved respiratory rate assessment, and better diagnostic tools. Furthermore, a shorter course of dispersible amoxicillin could potentially improve caregiver adherence, reducing risk of resistance and cost.
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http://dx.doi.org/10.1186/s12889-016-3541-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002323PMC
August 2016

Assessing the Quality of Care for Pneumonia in Integrated Community Case Management: A Cross-Sectional Mixed Methods Study.

PLoS One 2016 24;11(3):e0152204. Epub 2016 Mar 24.

Malaria Consortium, London, United Kingdom.

Background: Pneumonia is the leading infectious cause of mortality in children under five worldwide. Community-level interventions, such as integrated community case management, have great potential to reduce the burden of pneumonia, as well as other diseases, especially in remote populations. However, there are still questions as to whether community health workers (CHW) are able to accurately assess symptoms of pneumonia and prescribe appropriate treatment. This research addresses limitations of previous studies using innovative methodology to assess the accuracy of respiratory rate measurement by CHWs and provides new evidence on the quality of care given for children with symptoms of pneumonia. It is one of few that assesses CHW performance in their usual setting, with independent re-examination by experts, following a considerable period of time post-training of CHWs.

Methods: In this cross-sectional mixed methods study, 1,497 CHW consultations, conducted by 90 CHWs in two districts of Luapula province, Zambia, were directly observed, with measurement of respiratory rate for children with suspected pneumonia recorded by video. Using the video footage, a retrospective reference standard assessment of respiratory rate was conducted by experts. Counts taken by CHWs were compared against the reference standard and appropriateness of the treatment prescribed by CHWs was assessed. To supplement observational findings, three focus group discussions and nine in depth interviews with CHWs were conducted.

Results And Conclusion: The findings support existing literature that CHWs are capable of measuring respiratory rates and providing appropriate treatment, with 81% and 78% agreement, respectively, between CHWs and experts. Accuracy in diagnosis could be strengthened through further training and the development of improved diagnostic tools appropriate for resource-poor settings.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0152204PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4806924PMC
August 2016

Placental Plasmodium falciparum malaria infection: operational accuracy of HRP2 rapid diagnostic tests in a malaria endemic setting.

Malar J 2011 Oct 18;10:306. Epub 2011 Oct 18.

Malaria Consortium, Upper Naguru East Road, P,O, Box 8045, Kampala, Uganda.

Background: Malaria has a negative effect on the outcome of pregnancy. Pregnant women are at high risk of severe malaria and severe haemolytic anaemia, which contribute 60-70% of foetal and perinatal losses. Peripheral blood smear microscopy under-estimates sequestered placental infections, therefore malaria rapid diagnostic tests (RDTs) detecting histidine rich protein-2 antigen (HRP-2) in peripheral blood are a potential alternative.

Methods: HRP-2 RDTs accuracy in detecting malaria in pregnancy (MIP >28 weeks gestation) and placental Plasmodium falciparum malaria (after childbirth) were conducted using Giemsa microscopy and placental histopathology respectively as the reference standard. The study was conducted in Mbale Hospital, using the midwives to perform and interpret the RDT results. Discordant results samples were spot checked using PCR techniques.

Results: Among 433 febrile women tested, RDTs had a sensitivity of 96.8% (95% CI 92-98.8), specificity of 73.5% (95% CI 67.8-78.6), a positive predictive value (PPV) of 68.0% (95% CI 61.4-73.9), and negative predictive value (NPV) of 97.5% (95% CI 94.0-99.0) in detecting peripheral P. falciparum malaria during pregnancy. At delivery, in non-symptomatic women, RDTs had a 80.9% sensitivity (95% CI 57.4-93.7) and a 87.5% specificity (95%CI 80.9-92.1), PPV of 47.2% (95% CI 30.7-64.2) and NPV of 97.1% (95% CI 92.2-99.1) in detecting placental P. falciparum infections among 173 samples. At delivery, 41% of peripheral infections were detected by microscopy without concurrent placental infection. The combination of RDTs and microscopy improved the sensitivity to 90.5% and the specificity to 98.4% for detecting placental malaria infection (McNemar's X(2)> 3.84). RDTs were not superior to microscopy in detecting placental infection (McNemar's X(2)< 3.84). Presence of malaria in pregnancy and active placental malaria infection were 38% and 12% respectively. Placental infections were associated with poor pregnancy outcome [pre-term, still birth and low birth weight] (aOR = 37.9) and late pregnancy malaria infection (aOR = 20.9). Mosquito net use (aOR 2.1) and increasing parity (aOR 2.7) were associated with lower risk for malaria in pregnancy.

Conclusion: Use of HRP-2 RDTs to detect malaria in pregnancy in symptomatic women was accurate when performed by midwives. A combination of RDTs and microscopy provided the best means of detecting placental malaria. RDTs were not superior to microscopy in detecting placental infection. With a high sensitivity and specificity, RDTs could be a useful tool for assessing malaria in pregnancy, with further (cost-) effectiveness studies.
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http://dx.doi.org/10.1186/1475-2875-10-306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206496PMC
October 2011

Evaluation of three parasite lactate dehydrogenase-based rapid diagnostic tests for the diagnosis of falciparum and vivax malaria.

Malar J 2009 Oct 27;8:241. Epub 2009 Oct 27.

Epicentre, Paris, France.

Background: In areas where non-falciparum malaria is common rapid diagnostic tests (RDTs) capable of distinguishing malaria species reliably are needed. Such tests are often based on the detection of parasite lactate dehydrogenase (pLDH).

Methods: In Dawei, southern Myanmar, three pLDH based RDTs (CareStart Malaria pLDH (Pan), CareStart Malaria pLDH (Pan, Pf) and OptiMAL-IT)were evaluated in patients presenting with clinically suspected malaria. Each RDT was read independently by two readers. A subset of patients with microscopically confirmed malaria had their RDTs repeated on days 2, 7 and then weekly until negative. At the end of the study, samples of study batches were sent for heat stability testing.

Results: Between August and November 2007, 1004 patients aged between 1 and 93 years were enrolled in the study. Slide microscopy (the reference standard) diagnosed 213 Plasmodium vivax (Pv) monoinfections, 98 Plasmodium falciparum (Pf) mono-infections and no malaria in 650 cases. The sensitivities (sens) and specificities (spec), of the RDTs for the detection of malaria were- CareStart Malaria pLDH (Pan) test: sens 89.1% [CI95 84.2-92.6], spec 97.6% [CI95 96.5-98.4]. OptiMal-IT: Pf+/- other species detection: sens 95.2% [CI95 87.5-98.2], spec 94.7% [CI95 93.3-95.8]; non-Pf detection alone: sens 89.6% [CI95 83.6-93.6], spec 96.5% [CI95 94.8-97.7]. CareStart Malaria pLDH (Pan, Pf): Pf+/- other species: sens 93.5% [CI95 85.4-97.3], spec 97.4% [95.9-98.3]; non-Pf: sens 78.5% [CI95 71.1-84.4], spec 97.8% [CI95 96.3-98.7]. Inter-observer agreement was excellent for all tests (kappa > 0.9). The median time for the RDTs to become negative was two days for the CareStart Malaria tests and seven days for OptiMAL-IT. Tests were heat stable up to 90 days except for OptiMAL-IT (Pf specific pLDH stable to day 20 at 35 degrees C).

Conclusion: None of the pLDH-based RDTs evaluated was able to detect non-falciparum malaria with high sensitivity, particularly at low parasitaemias. OptiMAL-IT performed best overall and would perform best in an area of high malaria prevalence among screened fever cases. However, heat stability was unacceptable and the number of steps to perform this test is a significant drawback in the field. A reliable, heat-stable, highly sensitive RDT, capable of diagnosing all Plasmodium species has yet to be identified.
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http://dx.doi.org/10.1186/1475-2875-8-241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774865PMC
October 2009

Evaluation of three rapid tests for diagnosis of P. falciparum and P. vivax malaria in Colombia.

Am J Trop Med Hyg 2006 Dec;75(6):1209-15

Médecins sans Frontières (MSF), London, UK.

The diagnostic capacity of three malaria rapid diagnostic tests (RDTs), NOW-Malaria-ICT, OptiMAL-IT, and Paracheck-Pf, was evaluated against expert microscopy in Colombia. We tested 896 patients, of whom microscopy confirmed 139 P. falciparum, 279 P. vivax, and 13 mixed P.f/P.v infections and 465 negatives. Paracheck-Pf and NOW-malaria-ICT were more accurate in detecting P. falciparum (sensitivities 90.8% and 90.1%, respectively) in comparison with Optimal-IT (83.6%). NOW showed an acceptable Pf detection rate at low densities (< 500/microL), but resulted in a higher proportion of false positives. For P. vivax diagnosis, Optimal-IT had a higher sensitivity than NOW (91.0% and 81.4%, respectively). The choice between the two Pf/Pv detecting RDTs balances P. falciparum and P. vivax detection rates. Considering some degree of P. falciparum overtreatment and failure to detect all P. vivax cases as more acceptable than missing some cases of P. falciparum, we recommend careful implementation of NOW-malaria-ICT in areas where microscopy is lacking. The price is however still a constraint.
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December 2006
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