Anopheles funestus sensu stricto Giles (Diptera:Culicidae) bites after sunrise at two rural villages in northern Malawi and its implications for malaria vector control.

Introduction: Malawi has scaled up distribution and use of LLINs but their effectiveness depends on vector behaviour. This study reports information on where and when peak biting takes place by Anopheles vectors at two study sites in northern Malawi. Methods: The study was carried out at a single village each in Nkhata Bay and Karonga districts, northern Malawi. Monthly, three teams of four people each sampled mosquitoes using Human Landing Collections (HLCs) from 6.00 pm to 6.00 am. Mosquitoes were counted and identified by PCR. Plasmodium falciparum sporozoites were detected by ELISA and an entomological inoculation rate was estimated. Results: A total of 4,668 and 2,079 mosquitoes were sampled in Nkhata Bay and Karonga districts respectively. An. funestus s.s was common (91.3%; n = 2,611) in Nkhata Bay while An. arabiensis was common (96.9%; n = 706) in Karonga. Pf sporozoite rates varied from 0.8% (4/484) to 3.3% (51/1558). Individuals in Nkhata Bay received more bites (approx. 200 bites/ person/ night) compared to Karonga (approx. 50 bites/ person/ night). An. funestus was more likely to bite indoors (p=0.002) while An. arabiensis was (p=0.05) more likely to bite outdoors. Furthermore, An. funestus peak biting was in the early morning hours from 4:00 am (approx. 331 and 177 bites/ person/ night indoors and outdoors respectively) and remained high till 6:00 am. An. arabiensis peak biting (approx. 63 and 62 bites/ person/ night indoors and outdoors respectively) was around mid-night (12:00). An EIR of 108.4 infective bites/ person/ year was estimated for Nkhata Bay compared to 9.1 infective bites/ person/ year for Karonga. Conclusion: An. funestus s.s. had a considerable Pf sporozite infection rate and EIR. The shift in biting behaviour shown by this species poses a challenge to malaria control. Further studies are required to understand the biting behaviour of Anopheles vectors in Malawi.

Overdiagnosis of Malaria Illness in an Endemic Setting: A Facility-Based Surveillance Study in Malawi.

In endemic settings where asymptomatic malaria infections are common, malaria infection can complicate fever diagnosis. Factors influencing fever misdiagnosis, including accuracy of malaria rapid diagnostic tests (mRDTs) and the malaria-attributable fraction of fevers (MAF), require further investigation. We conducted facility-based surveillance in Malawi, from January 2012 through December 2013 in settings of high perennial (Chikhwawa), high seasonal (Thoylo), and moderate seasonal (Ndirande) malaria transmission. Consecutive patients presenting to outpatient departments were screened; those with suspected malaria illness were tested by mRDT or routine thick-smear microscopy. Test positivity rates (TPRs), positive predictive value (PPVs) of mRDTs, and MAFs were calculated by site, age, and season. Of 41,471 patients, 10,052 (24.2%) tested positive for malaria. The TPR was significantly greater in Chikhwawa (29.9%; 95% CI, 28.6-30.0) compared with Thyolo (13.2%; 95% CI, 12.5-13.7) and Ndirande (13.1%; 95% CI, 12.2-14.4). The overall PPV was 77.8% (95% CI, 76.8-78.7); it was lowest among infants (69.9%; 95% CI, 65.5-74.2) and highest among school-age children (81.9%; 95% CI, 80.3-83.4). Malaria infection accounted for about 50% of fevers in children younger than 5 years old with microscopy-confirmed Plasmodium falciparum infection, and less than 20% of such fevers in school-age children. Outpatient settings in Malawi had a high burden of malaria illness, but also possible overdiagnosis of malaria illness. Interventions to reduce malaria transmission and rapid testing for other common febrile illness may improve diagnostic clarity among outpatients in malaria endemic settings.

Prevalence and Clinical Management of Non-malarial Febrile Illnesses among Outpatients in the Era of Universal Malaria Testing in Malawi.

Increasing access to rapid diagnostic tests for malaria (mRDTs) has raised awareness of the challenges healthcare workers face in managing non-malarial febrile illnesses (NMFIs). We examined NMFI prevalence, clinical diagnoses, and prescribing practices in outpatient clinics across different malaria transmission settings in Malawi. Standardized facility-based malaria surveillance was conducted at three facilities one of every 4 weeks over 2 years. Information on demographics, presenting symptoms, temperature, clinical diagnosis, and treatment were collected from outpatients presenting with malaria-like symptoms. Of the 25,486 patients with fever, 69% had NMFI. Non-malarial febrile illness prevalence was lower in 5- to 15-year-old patients (55%) than in children < 5 years (72%) and adults > 15 years of age (77%). The most common clinical diagnoses among febrile patients with negative mRDTs in all age-groups and settings were respiratory infections (46%), sepsis (29%), gastroenteritis (13%), musculoskeletal pain (9%), and malaria (5%). Antibiotic prescribing was high in all age-groups and settings. Trimethoprim-sulfamethoxazole (40%) and amoxicillin (29%) were the most commonly prescribed antibiotics and were used for nearly all clinical diagnoses. In these settings with minimal access to diagnostic tools, patients with fever and a negative mRDT received a limited number of clinical diagnoses. Many were likely to be inaccurate and were associated with the inappropriate use of the limited range of available antibiotics. Prescription and diagnostic practices for NMFIs in the facilities require research and policy input. Resource-limited malaria-endemic countries urgently need more point-of-care diagnostic tools and evidence-based diagnosis and treatment algorithms to provide effective and cost-efficient care.

Impact of school-based malaria case management on school attendance, health and education outcomes: a cluster randomised trial in southern Malawi.

Introduction: Evidence indicates children who suffer from ill-health are less likely to attend or complete schooling. Malaria is an important cause of morbidity and mortality in school-age children. However, they are less likely to receive malaria treatment at health facilities and evidence for how to improve schoolchildren's access to care is limited. This study aimed to evaluate the impact of a programme of school-based malaria case management on schoolchildren's attendance, health and education. Methods: A cluster randomised controlled trial was conducted in 58 primary schools in Zomba District, Malawi, 2011-2015. The intervention, implemented in 29 randomly selected schools, provided malaria rapid diagnostic tests and artemisinin-based combination therapy to diagnose and treat uncomplicated malaria as part of basic first aid kits known as 'Learner Treatment Kits' (LTK). The primary outcome was school attendance, assessed through teacher-recorded daily attendance registers and independent periodic attendance spot checks. Secondary outcomes included prevalence of Plasmodium spp infection, anaemia, educational performance, self-reported child well-being and health-seeking behaviour. A total of 9571 children from standards 1-7 were randomly selected for assessment of school attendance, with subsamples assessed for the secondary outcomes. Results: Between November 2013 and March 2015, 97 trained teachers in 29 schools provided 32 685 unique consultations. Female schoolchildren were significantly more likely than male to seek a consultation (unadjusted OR=1.78 (95% CI 1.58 to 2.00). No significant intervention effect was observed on the proportion of child-days recorded as absent in teacher registers (n=9017 OR=0.90 (95% CI 0.77 to 1.05), p=0.173) or of children absent during random school visits-spot checks (n=5791 OR=1.09 (95% CI 0.87 to 1.36), p=0.474). There was no significant impact on child-reported well-being, prevalence of Plasmodium spp, anaemia or education scores. Conclusion: Despite high community demand, the LTK programme did not reduce schoolchildren's absenteeism or improve health or education outcomes in this study setting. Trial registration number: ClinicalTrials.gov NCT02213211.

Challenges in Treatment for Fever among School-Age Children and Adults in Malawi.

Prompt and effective treatment is key to malaria control and prevention, as it reduces disease morbidity and mortality and minimizes the number of transmission reservoirs. Transmission reduction may be particularly important among school-age children (SAC, 5-15 years old), who have the highest prevalence of Plasmodium falciparum infection in southern Malawi. We hypothesized that one factor contributing to this difference in prevalence is that SAC are less likely to seek appropriate treatment for fever than children younger than 5 years. In this study, we assessed treatment-seeking behaviors of people of all ages between 2012 and 2014 in Malawi. During each of the five cross-sectional surveys, all members of ∼900 households reported on fever and treatment-seeking in the previous 2 weeks. Multilevel logistic regression was used to analyze predictors of whether febrile people sought treatment and whether they did so at formal (government/private clinics) or informal sources (primarily shops). Twenty-two percent of participants (3,579/16,621) reported fever, and 2,715 of those (75.9%) sought treatment. Seeking treatment exclusively from local shops remains a common practice, although use of recommended diagnostic testing and antimalarial drugs was infrequently reported there. Although SAC were not significantly less likely than children aged < 5 years to seek treatment, SAC and adults (age ≥ 16 years) were significantly less likely to use formal sources. Our results indicate that encouraging treatment at government/private clinics and increasing retail access to appropriate antimalarial testing and treatment, especially among SAC, could help remedy inadequate treatment of symptomatic disease and potentially reduce Plasmodium transmission in Malawi.

Quality of Case Management for Pneumonia and Diarrhea Among Children Seen at Health Facilities in Southern Malawi.

Pneumonia and diarrhea are leading causes of child deaths in Malawi. Guidelines to manage childhood illnesses in resource-poor settings exist, but studies have reported low health-care worker (HCW) adherence to guidelines. We conducted a health facility survey from January to March 2015 to assess HCW management of pneumonia and diarrhea in children < 5 years of age in southern Malawi, and to determine factors associated with case management quality. Descriptive statistics and multivariable logistic regression models examined patient, HCW, and health facility factors associated with recommended pneumonia and diarrhea management, using Malawi's national guidelines as the gold standard. Of 694 surveyed children 2-59 months of age at 95 health facilities, 132 (19.0%) met survey criteria for pneumonia; HCWs gave recommended antibiotic treatment to 90 (68.2%). Of 723 children < 5 years of age, 222 (30.7%) had uncomplicated diarrhea; HCWs provided recommended treatment to 94 (42.3%). In multivariable analyses, caregivers' spontaneous report of children's symptoms was associated with recommended treatment of both pneumonia (odds ratio [OR]: 2.8, 95% confidence interval [CI]: 1.2-6.8, P = 0.023) and diarrhea (OR: 24.2, 95% CI: 6.0-97.0, P < 0001). Malaria diagnosis was negatively associated with recommended treatment (OR for pneumonia: 0.5, 95% CI: 0.2-1.0, P = 0.046; OR for diarrhea: 0.3, 95% CI: 0.1-0.6, P = 0.003). To improve quality of care, children should be assessed systematically, even when malaria is suspected. Renewed efforts to invigorate such a systematic approach, including HCW training, regular follow-up supervision, and monitoring HCW performance, are needed in Malawi.

Health worker adherence to malaria treatment guidelines at outpatient health facilities in southern Malawi following implementation of universal access to diagnostic testing.

BACKGROUND: Appropriate diagnosis and treatment are essential for reducing malaria mortality. A cross-sectional outpatient health facility (HF) survey was conducted in southern Malawi from January to March 2015 to determine appropriate malaria testing and treatment practices four years after implementation of a policy requiring diagnostic confirmation before treatment. METHODS: Enrolled patients were interviewed, examined and had their health booklet reviewed. Health workers (HWs) were asked about training, supervision and access to the 2013 national malaria treatment guidelines. HFs were assessed for malaria diagnostic and treatment capacity. Weighted descriptive analyses and logistic regression of patient, HW and HF characteristics related to testing and treatment were performed. RESULTS: An evaluation of 105 HFs, and interviews of 150 HWs and 2342 patients was completed. Of 1427 suspect uncomplicated malaria patients seen at HFs with testing available, 1072 (75.7%) were tested, and 547 (53.2%) tested positive. Testing was more likely if patients spontaneously reported fever (odds ratio (OR) 2.6; 95% confidence interval (CI) 1.7-4.0), headache (OR 1.5; 95% CI 1.1-2.1) or vomiting (OR 2.0; 95% CI 1.0-4.0) to HWs and less likely if they reported skin problems (OR 0.4; 95% CI 0.2-0.6). Altogether, 511 (92.7%) confirmed cases and 98 (60.3%) of 178 presumed uncomplicated malaria patients (at HFs without testing) were appropriately treated, while 500 (96.6%) of 525 patients with negative tests did not receive anti-malarials. Only eight (5.7%) suspect severe malaria patients received appropriate pre-referral treatment. Appropriate treatment was more likely for presumed uncomplicated malaria patients (at HFs without testing) with elevated temperature (OR 1.5/1 °C increase; 95% CI 1.1-1.9), who reported fever to HWs (OR 5.7; 95% CI 1.9-17.6), were seen by HWs with additional supervision visits in the previous 6 months (OR 1.2/additional visit; 95% CI 1.0-1.4), or were seen by older HWs (OR 1.1/year of age; 95% CI 1.0-1.1). CONCLUSIONS: Correct testing and treatment practices were reasonably good for uncomplicated malaria when testing was available. Pre-referral treatment for suspect severe malaria was unacceptably rare. Encouraging HWs to elicit and appropriately respond to patient symptoms may improve practices.

Feasibility, acceptability and impact of integrating malaria rapid diagnostic tests and pre-referral rectal artesunate into the integrated community case management programme. A pilot study in Mchinji district, Malawi.

BACKGROUND: The World Health Organization recommends that persons of all ages suspected of malaria should receive a parasitological confirmation of malaria by use of malaria rapid diagnostic test (RDT) at community level, and that rectal artesunate should be used as a pre-referral treatment for severe malaria to rapidly reduce parasitaemia. This paper reports on findings from a pilot study that assessed the feasibility, acceptability and effects of integrating RDTs and pre-referral rectal artesunate into the integrated Community Case Management programme in Malawi. METHODS: This study used mixed methods to collect information for this survey. Pre- and post-intervention, cross-sectional, household surveys were carried out. A review of integrated community case management reports, including supervision checklists was conducted. Quantitative data were collected in tablets running on open data kit software, and then data were transferred to STATA version 12 for analysis. For key indicators, proportions were calculated at 95% confidence intervals. Qualitative data were recorded onto digital recorders, translated into English and transcribed for analysis. RESULTS: Out of 86 observed RDT performances, a total of 83 (97%) were performed correctly with a proper disposal of sharps and biohazard wastes. Only two (2%) febrile children who had an RDT negative result were treated with artemether-lumefantrine, contrary to malaria treatment guidelines. Utilization of community health workers (CHWs) as a first source of care increased from (33.9%) (95% CI; 25.5-42.3) at baseline to (89.7%) (95% CI; 83.5-95.5) at end line in the intervention villages. There was a corresponding decrease in the proportion of caregivers that first sought care from informal sources from 12.9% (95% CI; 6.9-18.9) to 1.9% (95% CI; 0.9-4.4) in the intervention villages. Acceptability of the use of RDTs and pre-referral rectal artesunate at the community level was relatively high. CONCLUSION: Integration of RDTs and pre-referral rectal at artesunate community level is both feasible and acceptable. The strategy has the potential to increase and improve utilization of child health services at community level. However, this depends on the CHWs' skills and their availability in remote areas.

Clinical outcomes among febrile children aged 2 to 59 months with negative malaria rapid diagnostic test results in Mchinji District, Malawi.

BACKGROUND: Malawi malaria treatment guidelines recommend a definitive diagnosis, using a malaria rapid diagnostic test (mRDT), for all patients with fever or history of fever. Improving the management and outcomes of febrile children with negative mRDT results should be a priority. METHODS: Through a prospective cohort study designed to investigate clinical outcomes of children treated at the community level, we followed, for 7 days, children aged 2 to 59 months, who had negative mRDT results and were treated with antipyretic medication. Clinical outcomes were assessed on days 3 and 7 post-recruitment. RESULTS: The median age of recruited children was 19 months. Of the 285 children enrolled, 139 (48.8%) were females. Of the children for whom data were available for analysis, 95/236 (40.3%) had fever (temperature ≥ 37.5°C) at enrolment, and almost half of the sick children (125/268; 46.6%) had symptoms of upper respiratory tract infection. Most sick children (89.6%; 95% confidence interval, CI = 84.2 to 93.3) recovered, while 10.4% (95% CI: 6.7 to 15.8) were still sick by day 7 of follow-up. There were no deaths reported during the 7 days of follow-up. Being afebrile at enrolment (odds ratio, OR = 2.5; 95% CI = 1.1 to 6.0; P = 0.027) and sleeping under an insecticide-treated net (ITN) (OR = 2.7; 95% CI = 1.2 to 6.2; P = 0.011) were associated with recovery by day 7. In multivariable analysis, sleeping under an ITN the previous night was the only factor associated with recovery by day 7. Microscopy did not detect any malaria parasites in the blood of recruited children, at recruitment or on day 7. CONCLUSIONS: In this community-level study, the majority of febrile children with negative mRDT results recovered within 7 days of health worker consultation for a febrile illness, having only taken antipyretics.

The High Burden of Malaria in Primary School Children in Southern Malawi.

Malaria among school children has received increased attention recently, yet there remain few detailed data on the health and educational burden of malaria, especially in southern Africa. This paper reports a survey among school children in 50 schools in Zomba District, Malawi. Children were assessed for Plasmodium infection, anemia, and nutritional status and took a battery of age-appropriate tests of attention, literacy, and numeracy. Overall, 60.0% of children were infected with Plasmodium falciparum, 32.4% were anemic and 32.4% reported sleeping under a mosquito net the previous night. Patterns of P. falciparum infection and anemia varied markedly by school. In multivariable analysis, higher odds of P. falciparum infection were associated with younger age and being stunted, whereas lower odds were associated with reported net use, higher parental education, and socioeconomic status. The odds of anemia were significantly associated with P. falciparum infection, with a dose-response relationship between density of infection and odds of anemia. No clear relationship was observed between health status and cognitive and educational outcomes. The high burden of malaria highlights the need to tackle malaria among school children.