Assessment of pre-referral treatment for malaria, diarrhea, and pneumonia by rural community health workers in Southwestern Uganda: a cross-sectional study.

BACKGROUND: Pre-referral treatment aims to stabilize the child's condition before transferring them to a higher level of healthcare. This study explored pre-referral treatment for diarrhea, malaria and pneumonia in children U5. The study aims to assess pre-referral treatment practices among community health workers (CHWs) for children aged 2 to 59 months diagnosed with malaria, diarrhea, and pneumonia. METHODS: Conducted in 2023, this study employed a quantitative retrospective analysis of secondary data gathered from March 2014 to December 2018. Among the subjects, 171 patients received pre-referral treatment, serving as the foundation for categorical data analysis, presenting proportions and 95% confidence intervals across different categories. RESULTS: In this cohort, 90 (53%) of the 177 children U5 were male, and age distribution showed 39 (23%), 70 (41%), and 62 (36%) in the 2-11 months, 12-35 months, and 36-60 months categories, respectively. Rapid Diagnostic Test (RDT) malaria results indicated a negative outcome in 83(60%) and positive in 55 (40%) of cases. Symptomatically, 45 (26%) had diarrhea, 52 (30%) exhibited fast breathing, and 109 (63%) presented with fever. Furthermore, 59 (35%) displayed danger signs, while 104 (61%) sought medical attention within 24 h. CONCLUSION: The study analyzed a sample of 171 children under 5 years old to assess various characteristics and variables related to pre-referral treatment. The findings reveal notable proportions in gender distribution, age categories, RDT results, presence of diarrhea, fast breathing, fever, danger signs, and timely medical visits. The results highlight the need to strengthen pre-referral treatment interventions and enhance iCCM programs.

Management of children with danger signs in integrated community case management care in rural southwestern Uganda (2014-2018).

BACKGROUND: In integrated community case management (iCCM) care, community health workers (CHWs) provide home-based management of fever, diarrhea and fast breathing for children aged <5 y. The iCCM protocol recommends that children with danger signs for severe illness are referred by CHWs to health facilities within their catchment area. This study examines the management of danger signs by CHWs implementing iCCM in a rural context. METHODS: A retrospective observational study that examined clinical records for all patients with danger signs evaluated by CHWs from March 2014 to December 2018 was conducted. RESULTS: In total, 229 children aged <5 y had been recorded as having a danger sign during 2014-2018. Of these children, 56% were males with a mean age of 25 (SD 16.9) mo, among whom 78% were referred by the CHWs as per the iCCM protocol. The age category of 12 to 35 mo had the highest numbers of prereferred and referred cases (54% and 46%, respectively). CONCLUSIONS: CHWs play a key role in early symptomatic detection, prereferral treatment and early referral of children aged <5 y. Danger signs among children aged <5 y, if left untreated, can result in death. A high proportion of the children with danger signs were referred as per the iCCM protocol. Continuous CHW training is emphasized to reduce the number of referral cases that are missed. More studies need to focus on children aged 12-35 mo and why they are the most referred category. Policymakers should occasionally revise iCCM guidelines to detail the types of danger signs and how CHWs can address these.

Promptness in seeking treatment from Village Health workers for children under five years with malaria, diarrhoea and pneumonia in rural southwestern Uganda.

BACKGROUND: Village Health Workers (VHWs) in Uganda provide treatment for the childhood illness of malaria, pneumonia, and diarrhoea through the integrated community case management (iCCM) strategy. Under the strategy children under five years receive treatment for these illnesses within 24 h of onset of illness. This study examined promptness in seeking treatment from VHWs by children under five years with malaria, pneumonia, and diarrhoea in rural southwestern Uganda. METHODS: In August 2022, a database containing information from the VHWs patient registers over a 5-year study period was reviewed (2014-2018). A total of 18,430 child records drawn from 8 villages of Bugoye sub-county, Kasese district were included in the study. Promptness was defined a caregiver seeking treatment for a child from a VHW within 24 h of onset of illness. RESULTS: Sixty-four percent (64%) of the children included in the study sought treatment promptly. Children with fever had the highest likelihood of seeking prompt treatment (aOR = 1.93, 95% CI 1.80-2.06, p < 0.001) as compared to those with diarrhoea (aOR = 1.43, 95% CI 1.32-1.52, p < 0.001) and pneumonia (aOR = 1.33, 95% CI 1.24-1.42, p < 0.001). CONCLUSION: The findings provide further evidence that VHWs play a critical role in the treatment of childhood illness in rural contexts. However, the proportion of children seeking prompt treatment remains below the target set at the inception of the iCCM strategy, in Uganda. There is a need to continually engage rural communities to promote modification of health-seeking behaviour, particularly for children with danger signs. Evidence to inform the design of services and behaviour change communication, can be provided through undertaking qualitative studies to understand the underlying reasons for decisions about care-seeking in rural settings. Co-design with communities in these settings may increase the acceptability of these services.

Contribution of community health workers to the treatment of common illnesses among under 5-year-olds in rural Uganda.

BACKGROUND: The control of malaria, pneumonia, and diarrhoea is important for the reduction in morbidity and mortality among children under 5 years. Uganda has adopted the Integrated Community Case Management strategy using Community Health Workers (CHWs) to address this challenge. The extent and trend of these three conditions managed by the CHWs are not well documented. This study was done to describe the epidemiology and trends of the three common illnesses treated by the CHWs in Bugoye Sub-County in rural Uganda. METHODS: A retrospective review of monthly morbidity data for children less than 5 years of age for the period April 2014-December 2018 for CHWs in rural Bugoye Sub-County in Kasese district, Uganda was done. The total number reviewed was 18,430 records. The data were analysed using STATA version 14. RESULTS: In total male were 50.2% of the sample, pneumonia was the highest cause of illness among the infants (< 1 year), while malaria was the highest among the children 1 year-59 months. Infection with a single illness was the commonest recorded cause of presentation but there were some children recorded with multiple illnesses. All the CHWs were managing the three common illnesses among children under 5 years. The trend of the three common illnesses was changing from malaria to pneumonia being the commonest. Children aged 12-24 months and 25-59 months were at 2.1 times (95% CI 1.7-2.4) and 5.2 times (95% CI 4.6-5.9), respectively, more likely to get malaria but less likely to get pneumonia and diarrhoea. CONCLUSION: Community Health Workers in rural Uganda are contributing significantly to the management of all the three commonest illnesses among under-5 years-old children. The trend of the commonest illness is changing from malaria to pneumonia. Children under 1 year are at a higher risk of getting pneumonia and diarrhoea and at a lower risk of getting malaria.

Long-term quality of integrated community case management care for children in Bugoye Subcounty, Uganda: a retrospective observational study.

OBJECTIVE: Integrated community case management (iCCM) of childhood illness in Uganda involves protocol-based care of malaria, pneumonia and diarrhoea for children under 5 years old. This study assessed volunteer village health workers' (VHW) ability to provide correct iCCM care according to the national protocol and change in their performance over time since initial training. SETTING: VHWs affiliated with the Ugandan national programme provide community-based care in eight villages in Bugoye Subcounty, a rural area in Kasese District. The first cohort of VHWs began providing iCCM care in March 2013, the second cohort in July 2016. PARTICIPANTS: All children receiving iCCM care in 18 430 clinical encounters occurring between April 2014 and December 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: The descriptive primary outcome measure was the proportion of patients receiving overall correct care, defined as adherence to the iCCM protocol for the presenting condition (hereafter quality of care). The analytic primary outcome was change in the odds of receiving correct care over time, assessed using logistic regression models with generalised estimating equations. Secondary outcome measures included a set of binary measures of adherence to specific elements of the iCCM protocol. Preplanned and final measures were the same. RESULTS: Overall, VHWs provided correct care in 74% of clinical encounters. For the first cohort of VHWs, regression modelling demonstrated a modest increase in quality of care until approximately 3 years after their initial iCCM training (OR 1.022 per month elapsed, 95% CI 1.005 to 1.038), followed by a modest decrease thereafter (OR 0.978 per month, 95% CI 0.970 to 0.986). For the second cohort, quality of care was essentially constant over time (OR 1.007 per month, 95% CI 0.989 to 1.025). CONCLUSION: Quality of care was relatively constant over time, though the trend towards decreasing quality of care after 3 years of providing iCCM care requires further monitoring.

Measles outbreak in Western Uganda: a case-control study.

BACKGROUND: Measles outbreaks are prevalent throughout sub-Saharan Africa despite the preventive measures like vaccination that target under five-year-old children and health systems strengthening efforts like prioritizing the supply chain for supplies. Measles immunization coverage for Kasese district and Bugoye HC III in 2018 was 72 and 69%, respectively. This coverage has been very low and always marked red in the Red categorization (below the national target/poor performing) on the national league table indicators. The aim of this study was to assess the scope of the 2018-2019 measles outbreak and the associated risk factors among children aged 0-60 months in Bugoye sub-county, Kasese district, western Uganda. METHODS: We conducted a retrospective unmatched case-control study among children aged 0-60 months with measles (cases) who had either a clinical presentation or a laboratory confirmation (IgM positivity) presenting at Bugoye Health Centre III (BHC) or in the surrounding communities between December 2018 and October 2019.. Caregivers of the controls (whose children did not have measles) were selected at the time of data collection in July 2020. A modified CDC case investigation form was used in data collection. Quantitative data was collected and analyzed using Microsoft excel and STATA version 13. The children's immunization cards and health registers at BHC were reviewed to ascertain the immunization status of the children before the outbreak. RESULTS: An extended measles outbreak occurred in Bugoye, Uganda occured between December 2018 and October 2019. All 34 facility-based measles cases were documented to have had maculopapular rash, conjunctivitis, and cough. Also, the majority had fever (97%), coryza (94.1%), lymphadenopathy (76.5%), arthralgias (73.5%) and Koplik Spots (91.2%) as documented in the clinical registers. Similar symptoms were reported among 36 community-based cases. Getting infected even after immunized, low measles vaccination coverage were identified as the principal risk factors for this outbreak. CONCLUSION: Measles is still a significant problem. This study showed that this outbreak was associated with under-vaccination. Implementing a second routine dose of measles-rubella vaccine would not only increase the number of children with at least one dose but also boost the immunity of those who had the first dose.

Usage of and satisfaction with Integrated Community Case Management care in western Uganda: a cross-sectional survey.

BACKGROUND: In some areas of Uganda, village health workers (VHW) deliver Integrated Community Case Management (iCCM) care, providing initial assessment of children under 5 years of age as well as protocol-based treatment of malaria, pneumonia, and diarrhoea for eligible patients. Little is known about community perspectives on or satisfaction with iCCM care. This study examines usage of and satisfaction with iCCM care as well as potential associations between these outcomes and time required to travel to the household's preferred health facility. METHODS: A cross-sectional household survey was administered in a rural subcounty in western Uganda during December 2016, using a stratified random sampling approach in villages where iCCM care was available. Households were eligible if the household contained one or more children under 5 years of age. RESULTS: A total of 271 households across 8 villages were included in the final sample. Of these, 39% reported that it took over an hour to reach their preferred health facility, and 73% reported walking to the health facility; 92% stated they had seen a VHW for iCCM care in the past, and 55% had seen a VHW in the month prior to the survey. Of respondents whose households had sought iCCM care, 60% rated their overall experience as "very good" or "excellent," 97% stated they would seek iCCM care in the future, and 92% stated they were "confident" or "very confident" in the VHW's overall abilities. Longer travel time to the household's preferred health facility did not appear to be associated with higher propensity to seek iCCM care or higher overall satisfaction with iCCM care. CONCLUSIONS: In this setting, community usage of and satisfaction with iCCM care for malaria, pneumonia, and diarrhoea appears high overall. Ease of access to facility-based care did not appear to impact the choice to access iCCM care or satisfaction with iCCM care.

A cross-sectional study comparing case scenarios and record review to measure quality of Integrated Community Case Management care in western Uganda.

BACKGROUND: In Integrated Community Case Management (iCCM), village health workers (VHW) assess and treat malaria, pneumonia and diarrhea using a clinical algorithm. Study objectives included: 1) Compare VHWs' performance on case scenario exercises to record review data; 2) assess impact of formal education on performance in the case scenario exercises. METHODS: 36 VHWs in Bugoye Subcounty, Uganda completed the case scenarios exercise, which included video case scenarios and brief oral case vignettes, between July 2017 and February 2018. We obtained clinical records for all iCCM encounters in the same time period. RESULTS: In the video case scenarios, 45% of mock patients received all correct management steps (including all recommended education), while 94% received all critical management steps. Based on the level of data available from record review, 74% of patients in the record review dataset received overall correct management compared to 94% in the video case scenarios. In the case scenarios, VHWs with primary school education performed similarly to those with some or all secondary school education. CONCLUSIONS: The case scenarios produced higher estimates of quality of care than record review. VHWs often omitted recommended health education topics in the case scenarios. Level of formal education did not appear to influence performance in the case scenarios.

Assessing Village Health Workers' Ability to Perform and Interpret Rapid Diagnostic Tests for Malaria 4 Years after Initial Training: A Cross-Sectional Study.

Village health workers (VHWs) in Bugoye subcounty, Uganda, provide integrated community case management (iCCM) care to children younger than 5 years for malaria, pneumonia, and diarrhea. We assessed the longevity of VHWs' skills in performing and reading malaria rapid diagnostic tests (RDTs) 4 years after initial training, comparing VHWs who had completed initial iCCM training 1 year before the study with VHWs who had completed training 4 years before the study. Both groups received quarterly refresher trainings. Trained interviewers observed 36 VHWs reading six mock RDTs each and performing an RDT as part of a larger skills assessment exercise. VHWs read 97% of mock RDTs correctly; of the 36 VHWs, 86% read all six mock RDTs correctly. Most VHWs scored either 12/13 or 13/13 on the RDT checklist (39% and 36%, respectively), with 25% scoring 11/13 or lower. For reading mock RDTs, VHWs in the first group (initial training 4 years before study) read 97% of mock RDTs correctly, whereas those in the second group (initial training 1 year before study) read 96% of mock RDTs correctly; the first group had a mean of 5.83 RDTs read correctly, compared with 5.77 RDTs read correctly in the second group (P = 0.83). For performing an RDT, the first group completed a mean of 12.0 steps correctly, compared with a mean of 12.2 correct steps in the second group (P = 0.60). Overall, VHWs demonstrated proficiency in reading RDTs accurately and performing RDTs according to protocol at least 4 years after initial iCCM training.

Dengue in Western Uganda: a prospective cohort of children presenting with undifferentiated febrile illness.

BACKGROUND: The spatial distribution and burden of dengue in sub-Saharan Africa remains highly uncertain, despite high levels of ecological suitability. The goal of this study was to describe the epidemiology of dengue among a cohort of febrile children presenting to outpatient facilities located in areas of western Uganda with differing levels of urbanicity and malaria transmission intensity. METHODS: Eligible children were first screened for malaria using rapid diagnostic tests. Children with a negative malaria result were tested for dengue using a combination NS1/IgM/IgG rapid test (SD Bioline Dengue Duo). Confirmatory testing by RT-PCR was performed in a subset of participants. Antigen-capture ELISA was performed to estimate seroprevalence. RESULTS: Only 6 of 1416 (0.42%) children had a positive dengue rapid test, while none of the RT-PCR results were positive. ELISA testing demonstrated reactive IgG antibodies in 28 (2.2%) participants with the highest prevalence seen at the urban site in Mbarara (19 of 392, 4.9%, p < 0.001). CONCLUSIONS: Overall, these findings suggest that dengue, while present, is an uncommon cause of non-malarial, pediatric febrile illness in western Uganda. Further investigation into the eocological factors that sustain low-level transmission in urban settings are urgently needed to reduce the risk of epidemics.

Prevalence of Molecular Markers of Antimalarial Drug Resistance across Altitudinal Transmission Zones in Highland Western Uganda.

We explored spatial variation in the prevalence of established molecular markers of antimalarial resistance across a geographically diverse, highland region of western Uganda. We identified Plasmodium falciparum CQ resistance transporter 76T mutations in all pools, but there was no evidence of spatial differences across village-based strata defined by either altitude or river valley. In contrast, we identified a significant inverse association between altitude and the prevalence of Plasmodium falciparum multidrug resistance 1 mutations with the largest proportion of Y184F mutations observed in the low-elevation, high-transmission villages. These results demonstrate the substantial heterogeneity in resistance markers observed across geographic settings, even at relatively small scales, but highlight the complex nature of these ecological relationships.

Completion of community health worker initiated patient referrals in integrated community case management in rural Uganda.

BACKGROUND: Uganda has sought to address leading causes of childhood mortality: malaria, pneumonia and diarrhoea, through integrated community case management (iCCM). The success of this approach relies on community health worker (CHW) assessment and referral of sick children to a nearby health centre. This study aimed to determine rates of referral completion in an iCCM programme in rural Uganda. METHODS: This was a prospective observational study of referrals made by CHWs in 8 villages in rural western Uganda. All patient referrals by CHWs were tracked and health centre registers were reviewed for documentation of completed referrals. Caregivers of referred patients were invited to complete a survey 2-3 weeks after the referral with questions on the CHW visit, referral completion, and the patient's clinical condition. RESULTS: Among 143 total referrals, 136 (94%) caregivers completed the follow-up survey. Reasons for visiting the CHW were fever/malaria in 111 (82%) cases, cough in 61 (45%) cases, and fast/difficult breathing in 25 (18%) cases. Overall, 121 (89%) caregivers reported taking the referred child for further medical evaluation, of whom 102 (75% overall) were taken to the local public health centre. Ninety per cent of reported referral visits were confirmed in health centre documentation. For the 34 caregivers who did not complete referral at the local health centre, the most common reasons were improvement in child's health, lack of time, ease of going elsewhere, and needing to care for other children. Referrals were slightly more likely to be completed on weekdays versus weekends (p = 0.0377); referral completion was otherwise not associated with child's age or gender, caregiver age, or caregiver relationship to child. One village had a lower rate of referral completion than the others. Improvement in the child's health was not associated with completed referral or timing of the referral visit. CONCLUSIONS: A high percentage of children referred to the health centre through iCCM in rural Uganda completed the referral. Barriers to referral completion included improvement in the child's health, time and distance. Interestingly, referral completion at the health centre was not associated with improvement in the child's health. Barriers to referral completion and clinical management at all stages of referral linkages warrant further study.

Private sector drug shops frequently dispense parenteral anti-malarials in a rural region of Western Uganda.

BACKGROUND: Malaria is a leading cause of paediatric morbidity and mortality in Uganda. More than half of febrile children in rural areas initially seek care at private clinics and drug shops. These shops are generally unregulated and the quality of clinical care is variable, with the potential for misdiagnosis and the development of drug resistance. There is thus an urgent need to identify rural drug shops and coordinate their malaria treatment efforts with those of the public sector. The objective of the study was to identify all drug shops in the Bugoye sub-county of Western Uganda and assess their anti-malarial dispensing practices. METHODS: This study is a cross-sectional survey of drug shops in a rural sub-county of Western Uganda. In the first phase, shop locations, licensing and shopkeeper's qualifications, and supply and pricing of anti-malarials were characterized. In the second phase, the proportion of anti-malarials dispensed by private drug shops was compared to public health facilities. RESULTS: A total of 48 drug shops were identified. Only one drug shop (1 of 48, 2%) was licensed with the sub-county's records office. The drug shops stocked a variety of anti-malarials, including first-line therapies and less effective agents (e.g., sulfadoxine/pyrimethamine). Almost all drug shops (45 of 48, 94%) provided parenteral anti-malarials. Of the 3900 individuals who received anti-malarials during the study, 2080 (53.3%) purchased anti-malarials through the private sector compared to 1820 (46.7%) who obtained anti-malarials through the public sector. Drug shops were the primary source of parenteral anti-malarials. Inadequate dosing of anti-malarials was more common in drug shops. CONCLUSIONS: Drug shops are major sources of parenteral anti-malarials, which should be reserved for cases of severe malaria. Strengthening malaria case management and incorporating drug shops in future interventions is necessary to optimize malaria control efforts in the sub-county, and in similarly endemic regions.

Who Stays and Who Goes: Predictors of Admission among Patients Presenting with Febrile Illness and a Positive Malaria Rapid Diagnostic Test in a Rural Ugandan Health Center.

Not much is known about clinical decision-making in rural, low-resource settings regarding fever, a common reason for presentation to care. In this prospective cohort study of patients presenting with febrile illness to a rural Ugandan health center, we examined demographic and clinical factors predictive of an initial disposition of inpatient admission after clinical evaluation, but before laboratory testing. We then assessed the association of laboratory results and system factors with a change between initial and final disposition plans. Four thousand nine hundred twenty-four patients with suspected febrile illness were included in the primary analysis. The strongest predictors for an initial disposition of admission after clinical examination were impaired consciousness (adjusted risk ratio [aRR], 3.21; 95% confidence interval [CI]: 2.44-4.21) and fever on examination (aRR, 2.27; 95% CI: 1.79-2.87). Providers initially planned to discharge patients with significant vital sign abnormalities, including tachypnea (3.6%) and hypotension (1.3%). Anemia strongly predicted a final disposition of admission after an initial disposition of discharge (aRR, 48.34; 95% CI: 24.22-96.49); other laboratory abnormalities, including hypoglycemia and acidosis, did not change disposition planning. In those with an initial disposition of admission, living farther than the two neighboring villages was associated with a final disposition of discharge (aRR, 2.12; 95% CI: 1.10-4.12). A concerning number of patients with abnormal vital signs and laboratory results were not admitted for inpatient care. Geographic factors may influence a patient's final disposition contrary to a provider's initial disposition plan. Future work should assess longer term outcomes after discharge and a broader study population.

Reuse of malaria rapid diagnostic tests for amplicon deep sequencing to estimate Plasmodium falciparum transmission intensity in western Uganda.

Molecular techniques are not routinely employed for malaria surveillance, while cross-sectional, community-based parasite surveys require significant resources. Here, we describe a novel use of malaria rapid diagnostic tests (RDTs) collected at a single facility as source material for sequencing to esimtate malaria transmission intensity across a relatively large catchment area. We extracted Plasmodium falciparum DNA from RDTs, then amplified and sequenced a region of the apical membrane antigen 1 (pfama1) using targeted amplicon deep sequencing. We determined the multiplicity of infection (MOI) for each sample and examined associations with demographic, clinical, and spatial factors. We successfully genotyped 223 of 287 (77.7%) of the samples. We demonstrated an inverse relationship between the MOI and elevation with individuals presenting from the highest elevation villages harboring infections approximately half as complex as those from the lowest (MOI 1.85 vs. 3.51, AOR 0.25, 95% CI 0.09-0.65, p = 0.004). This study demonstrates the feasibility and validity of using routinely-collected RDTs for molecular surveillance of malaria and has real-world utility, especially as the cost of high-throughpout sequencing continues to decline.

Quality of care in integrated community case management services in Bugoye, Uganda: a retrospective observational study.

BACKGROUND: Village health workers (VHWs) in five villages in Bugoye subcounty (Kasese District, Uganda) provide integrated community case management (iCCM) services, in which VHWs evaluate and treat malaria, pneumonia, and diarrhoea in children under 5 years of age. VHWs use a "Sick Child Job Aid" that guides them through the evaluation and treatment of these illnesses. A retrospective observational study was conducted to measure the quality of iCCM care provided by 23 VHWs in 5 villages in Bugoye subcounty over a 2-year period. METHODS: Patient characteristics and clinical services were summarized using existing aggregate programme data. Lot quality assurance sampling of individual patient records was used to estimate adherence to the iCCM algorithm, VHW-level quality (based on adherence to the iCCM protocol), and change over time in quality of care (using generalized estimating equations regression modelling). RESULTS: For each of 23 VHWs, 25 patient visits were randomly selected from a 2-year period after iCCM care initiation. In these visits, 97% (150) of patients with diarrhoea were treated with oral rehydration and zinc, 95% (216) of patients with pneumonia were treated with amoxicillin, and 94% (240) of patients with malaria were treated with artemisinin-based combination therapy or rectal artesunate. However, only 44% (44) of patients with a negative rapid test for malaria were appropriately referred to a health facility. Overall, 75% (434) of patients received all the correct evaluation and management steps. Only 9 (39%) of the 23 VHWs met the pre-determined LQAS threshold for high-quality care over the 2-year observation period. Quality of care increased significantly in the first 6 months after initiation of iCCM services (p = 0.003), and then plateaued during months 7-24. CONCLUSIONS: Quality of care was high for uncomplicated malaria, pneumonia and diarrhoea. Overall quality of care was lower, in part because VHWs often did not follow the guidelines to refer patients with fever who tested negative for malaria. Quality of care appears to improve in the initial months after iCCM implementation, as VHWs gain initial experience in iCCM care.

Anemia was an Uncommon Complication of Severe Malaria in a High-Transmission Rural Area of Western Uganda.

The clinical epidemiology of severe malaria among patients presenting to peripheral health centers has not been well described. We conducted a prospective, observational cohort study to describe the epidemiology and clinical manifestations of severe malaria in a highland area of declining transmission intensity in Western Uganda. Individuals presenting with a history of fever were screened with a malaria rapid diagnostic test (RDT). We prepared blood smears and conducted clinical and laboratory testing for those with a positive RDT. We defined severe malaria in accordance with World Health Organization guidelines for research and epidemiological studies. A total of 6,641 individuals underwent testing for malaria. Ninety-six of 1,462 (6.6%) participants with confirmed parasitemia satisfied the criteria for severe malaria. The incidence of severe malaria peaked between 2 and 3 years of age (incidence rate ratio = 17.1, 95% confidence interval = 8.4-34.9, P < 0.001) and then declined steadily until age 10. However, we also found a second peak among those ≥ 50 years of age. Severe anemia was uncommon, detected in only 5.3% of cases. Instead, shock (22.2%) and lactic acidosis (19.4%) were most frequently encountered. Our results suggest that the clinical characteristics of severe malaria presenting to rural, peripheral health centers may be different than previously observed in referral centers. These findings merit further investigation into the optimal methods for identification and management of severe malaria in rural health centers in the region.

Use of a Dual-Antigen Rapid Diagnostic Test to Screen Children for Severe Plasmodium falciparum Malaria in a High-Transmission, Resource-Limited Setting.

BACKGROUND: In rural areas, many patients with malaria seek care at peripheral health facilities or community case management programs. While this strategy is effective for the management of uncomplicated malaria, severe malaria necessitates prompt detection and referral to facilities with adequate resources. METHODS: In this prospective, observational cohort study, we assessed the accuracy of a dual-band (histidine-rich protein-2/pan-lactate dehydrogenase [HRP2/pLDH]) rapid diagnostic test (RDT) to differentiate uncomplicated from severe malaria. We included children aged <12 years who presented to a rural clinic in western Uganda with a positive HRP2 or HRP2/pLDH RDT. We estimated the test characteristics of a dual-antigen (HRP2+/pLDH+) band positive RDT compared to World Health Organization-defined clinical and laboratory criteria to detect severe malaria. RESULTS: A total of 2678 children underwent testing for malaria with an RDT, and 83 (9.0%) satisfied criteria for severe malaria. The sensitivity and specificity of a HRP2+/pLDH+ result for severe malaria was 97.6% (95% confidence interval [CI], 90.8%-99.6%) and 75.6% (95% CI, 73.8%-77.4%), respectively. An HRP2+/pLDH+ result was significantly more sensitive (97.6% vs 68.7%, P < .001) for the detection of severe malaria compared to algorithms that incorporate screening for danger signs. CONCLUSIONS: A positive dual-antigen (HRP2/pLDH) RDT has higher sensitivity than the use of clinical manifestations to detect severe malaria, making it a promising tool in the triage of children with malaria in low-resource settings. Additional work is needed to operationalize diagnostic and treatment algorithms that include dual-antigen RDTs to avoid over referral.

Improving the Specificity of Plasmodium falciparum Malaria Diagnosis in High-Transmission Settings with a Two-Step Rapid Diagnostic Test and Microscopy Algorithm.

Poor specificity may negatively impact rapid diagnostic test (RDT)-based diagnostic strategies for malaria. We performed real-time PCR on a subset of subjects who had undergone diagnostic testing with a multiple-antigen (histidine-rich protein 2 and pan-lactate dehydrogenase pLDH [HRP2/pLDH]) RDT and microscopy. We determined the sensitivity and specificity of the RDT in comparison to results of PCR for the detection of Plasmodium falciparum malaria. We developed and evaluated a two-step algorithm utilizing the multiple-antigen RDT to screen patients, followed by confirmatory microscopy for those individuals with HRP2-positive (HRP2+)/pLDH-negative (pLDH-) results. In total, dried blood spots (DBS) were collected from 276 individuals. There were 124 (44.9%) individuals with an HRP2+/pLDH+ result, 94 (34.1%) with an HRP2+/pLDH- result, and 58 (21%) with a negative RDT result. The sensitivity and specificity of the RDT compared to results with real-time PCR were 99.4% (95% confidence interval [CI], 95.9 to 100.0%) and 46.7% (95% CI, 37.7 to 55.9%), respectively. Of the 94 HRP2+/pLDH- results, only 32 (34.0%) and 35 (37.2%) were positive by microscopy and PCR, respectively. The sensitivity and specificity of the two-step algorithm compared to results with real-time PCR were 95.5% (95% CI, 90.5 to 98.0%) and 91.0% (95% CI, 84.1 to 95.2), respectively. HRP2 antigen bands demonstrated poor specificity for the diagnosis of malaria compared to that of real-time PCR in a high-transmission setting. The most likely explanation for this finding is the persistence of HRP2 antigenemia following treatment of an acute infection. The two-step diagnostic algorithm utilizing microscopy as a confirmatory test for indeterminate HRP2+/pLDH- results showed significantly improved specificity with little loss of sensitivity in a high-transmission setting.

Severe Flooding and Malaria Transmission in the Western Ugandan Highlands: Implications for Disease Control in an Era of Global Climate Change.

BACKGROUND: There are several mechanisms by which global climate change may impact malaria transmission. We sought to assess how the increased frequency of extreme precipitation events associated with global climate change will influence malaria transmission in highland areas of East Africa. METHODS: We used a differences-in-differences, quasi-experimental design to examine spatial variability in the incidence rate of laboratory-confirmed malaria cases and malaria-related hospitalizations between villages (1) at high versus low elevations, (2) with versus without rivers, and (3) upstream versus downstream before and after severe flooding that occurred in Kasese District, Western Region, Uganda, in May 2013. RESULTS: During the study period, 7596 diagnostic tests were performed, and 1285 patients were admitted with a diagnosis of malaria. We observed that extreme flooding resulted in an increase of approximately 30% in the risk of an individual having a positive result of a malaria diagnostic test in the postflood period in villages bordering a flood-affected river, compared with villages farther from a river, with a larger relative impact on upstream versus downstream villages (adjusted rate ratio, 1.91 vs 1.33). CONCLUSIONS: Extreme precipitation such as the flooding described here may pose significant challenges to malaria control programs and will demand timely responses to mitigate deleterious impacts on human health.