Plasmodium falciparum genetic diversity and multiplicity of infection based on msp-1, msp-2, glurp and microsatellite genetic markers in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: In sub-Saharan Africa (SSA), Plasmodium falciparum causes most of the malaria cases. Despite its crucial roles in disease severity and drug resistance, comprehensive data on Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are sparse in SSA. This study summarizes available information on genetic diversity and MOI, focusing on key markers (msp-1, msp-2, glurp, and microsatellites). The systematic review aimed to evaluate their influence on malaria transmission dynamics and offer insights for enhancing malaria control measures in SSA. METHODS: The review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Two reviewers conducted article screening, assessed the risk of bias (RoB), and performed data abstraction. Meta-analysis was performed using the random-effects model in STATA version 17. RESULTS: The review included 52 articles: 39 cross-sectional studies and 13 Randomized Controlled Trial (RCT)/cohort studies, involving 11,640 genotyped parasite isolates from 23 SSA countries. The overall pooled mean expected heterozygosity was 0.65 (95% CI: 0.51-0.78). Regionally, values varied: East (0.58), Central (0.84), Southern (0.74), and West Africa (0.69). Overall pooled allele frequencies of msp-1 alleles K1, MAD20, and RO33 were 61%, 44%, and 40%, respectively, while msp-2 I/C 3D7 and FC27 alleles were 61% and 55%. Central Africa reported higher frequencies (K1: 74%, MAD20: 51%, RO33: 48%) than East Africa (K1: 46%, MAD20: 42%, RO33: 31%). For msp-2, East Africa had 60% and 55% for I/C 3D7 and FC27 alleles, while West Africa had 62% and 50%, respectively. The pooled allele frequency for glurp was 66%. The overall pooled mean MOI was 2.09 (95% CI: 1.88-2.30), with regional variations: East (2.05), Central (2.37), Southern (2.16), and West Africa (1.96). The overall prevalence of polyclonal Plasmodium falciparum infections was 63% (95% CI: 56-70), with regional prevalences as follows: East (62%), West (61%), Central (65%), and South Africa (71%). CONCLUSION: The study shows substantial regional variation in Plasmodium falciparum parasite genetic diversity and MOI in SSA. These findings suggest a need for malaria control strategies and surveillance efforts considering regional-specific factors underlying Plasmodium falciparum infection.

Village health team-delivered oral HIV self-testing increases linkage-to-care and antiretroviral-therapy initiation among men in Uganda.

Targeted strategies are central to increasing HIV-status awareness and progress on the care cascade among men. We implemented Village-Health-Team (VHT)-delivered HIV self-testing (HIVST) among men in a peri-urban Ugandan district and assessed linkage to confirmatory-testing, antiretroviral-therapy (ART) initiation and HIV-status disclosure following HIVST. We conducted a prospective cohort study from November 2018 to June 2019 and enrolled 1628 men from 30-villages of Mpigi district. VHTs offered each participant one HIVST-kit and a linkage-to-care information leaflet. At baseline, we collected data on demographics, testing history and risk behavior. At one-month, we measured linkage to confirmatory-testing and HIV-status disclosure, and at three months ART-initiation if tested HIV-positive. We used Poisson regression generalized estimating equations to evaluate predictors of confirmatory-testing. We found that 19.8% had never tested for HIV and 43% had not tested in the last 12-months. After receiving HIVST-kits, 98.5% self-reported HIVST-uptake in 10-days, 78.8% obtained facility-based confirmation in 30-days of HIVST with 3.9% tested HIV-positive. Of the positives, 78.8% were newly diagnosed, 88% initiated ART and 57% disclosed their HIV-status to significant others. Confirmatory testing was associated with having a higher level of education and knowing a partner's HIV-status. VHT-delivered HIVST may be effective for boosting testing, ART-initiation and HIV-status disclosure among men.

The clinical utility of cystatin C based eGFR in assessing renal function among HIV/AIDs patients on ART at Mildmay Uganda.

BACKGROUND: In clinical practice, Measurement of estimated glomerular filtration rates (eGFR) is the gold standard assessing renal function the glomerular filtration rate often estimated from plasma creatinine. Several studies have shown Cystatin C based eGFR (Cys C) to be a better parameter for the diagnosis of impaired renal function. Cystatin C based eGFR has been proposed as a potential renal function marker but its use in HIV&AIDS patients has not been well evaluated. METHODS: A cross sectional study was carried out on 914 HIV&AIDS patients on antiretroviral therapy (ART) attending Mildmay Uganda for care and treatment between January to March 2015. Serum Cystatin C based eGFR was measured using the particle enhanced immunoturbidimetric assay. Creatinine was analyzed using enzymatic Creatinine PAP method and creatinine clearance was calculated according to C&G. RESULTS: The sensitivity of Cystatin C based eGFR was 15.1% (95% CI = 8.4, 24) with specificity 99.3% (95% CI = 98- 99.7). The positive and negative predictive values were 70.0% (95% CI 45.7-88.1) and 91.2% (95% CI 98.11-92.94) respectively. The positive likelihood ratio was 18.81 and negative likelihood ratio was 0.85. Cystatin C based eGFR had diagnostic accuracy of 90.7 and area under curve was 0.768. CONCLUSION: Cystatin C based eGFR exhibited a high specificity and a high positive likelihood ratio in diagnosis of kidney disease among HIV&AIDS patients. Cystatin C based eGFR can be used as a confirmatory test.

Adherence to malaria management guidelines by health care workers in the Busoga sub-region, eastern Uganda.

BACKGROUND: Appropriate malaria management is a key malaria control strategy. The objective of this study was to determine health care worker adherence levels to malaria case management guidelines in the Busoga sub-region, Uganda. METHODS: Health facility assessments, health care worker (HCW), and patient exit interview (PEI) surveys were conducted at government and private health facilities in the sub-region. All health centres (HC) IVs, IIIs, and a sample of HC IIs, representative of the tiered structure of outpatient service delivery at the district level were targeted. HCWs at these facilities were eligible for participation in the study. For PEIs, 210 patients of all ages presenting with a history of fever for outpatient care at selected facilities in each district were targeted. Patient outcome measures included testing rates, adherence to treatment, dispensing and counselling services as per national guidelines. The primary outcome was appropriate malaria case management, defined as the proportion of patients tested and only prescribed artemether-lumefantrine (AL) if positive. HCW readiness (e.g., training, supervision) and health facility capacity (e.g. availability of diagnostics and anti-malarials) to provide malaria case management were also assessed. Data were weighted to cater for the disproportionate representation of HC IIs in the study sample. RESULTS: A total of 3936 patients and 1718 HCW from 392 facilities were considered in the analysis. The median age of patients was 14 years; majority (63.4%) females. Most (70.1%) facilities were HCIIs and 72.7% were owned by the government. Malaria testing services were available at > 85% of facilities. AL was in stock at 300 (76.5%) facilities. Of those with a positive result, nearly all were prescribed an anti-malarial, with AL (95.1%) accounting for most prescriptions. Among those prescribed AL, 81.0% were given AL at the facility, lowest at HC IV (60.0%) and government owned (80.1%) facilities, corresponding to AL stock levels. Overall, 86.9% (95%CI 79.7, 90.7) of all enrolled patients received appropriate malaria case management. However, only 50.7% (21.2, 79.7) of patients seen at PFPs received appropriate malaria management. CONCLUSION: Adherence levels to malaria case management guidelines were good, but with gaps noted mainly in the private sector. The supply chain for AL needs to be strengthened. Interventions to improve practise at PFP facilities should be intensified.

Quality of care for adult in-patients with malaria in a tertiary hospital in Uganda.

BACKGROUND: Prompt detection and appropriate treatment of malaria prevents severe disease and death. The quality of care for adult malaria in-patients is not well documented in sub-Saharan Africa, particularly in Uganda. The study sought to describe the patterns of malaria diagnosis and treatment among adult in-patients admitted to the medical and gynaecological wards of Uganda's 1790-bed Mulago National Referral Hospital from December 2013 to April 2014. METHODS: A prospective cohort of 762 consented in-patients aged ≥ 18 years was assembled. Proportions of in-patients who received preadmission and in-hospital anti-malarials, missed Day 1 dosing of hospital-initiated anti-malarials and/or had malaria microscopy done were determined. Multivariable logistic regression was used to identify risk-factors for missed Day 1 dosing of anti-malarials. RESULTS: One in five (19%, 146/762) in-patients had an admission or discharge malaria diagnosis or both; with median age of 29 years (IQR, 22-42 years). Microscopy was requested in 77% (108/141) of in-patients with an admission malaria diagnosis; results were available for 46% (50/108), of whom 42% (21/50) tested positive for Plasmodium falciparum malaria parasitaemia. Only 13% (11/83) of in-patients who received in-hospital injectable artesunate (AS) or quinine (Q) received follow-up oral artemether-lumefantrine (AL); 2 of 18 severe malaria cases received follow-up oral AL. Injectable AS only (47%, 47/100) was the most frequent hospital-initiated anti-malarial treatment followed by injectable Q only (23%, 23/100) amongst in-patients who received in-hospital anti-malarials. A quarter (25%, 25/100; 95% CI: 17-35%) of in-patients missed Day 1 dosing of hospital-initiated anti-malarials. Each additional admission diagnosis was more than two-fold likely to increase the odds of missed Day 1 dosing of in-hospital anti-malarials (aOR = 2.6, 95% CI: 1.52-4.56; P-value = 0.001). CONCLUSIONS: Half the malaria microscopy results were not available; yet, the rate of testing was high. The majority of in-patients initiated on injectable AS or Q did not receive the recommended follow-up oral AL. One in four in-patients delayed to initiate hospital anti-malarials by at least one calendar day. The hospital should encourage prompt availability of malaria test-results to promote the timely initiation and completion of anti-malarial treatment, thereby improving the quality of care for hospitalized malaria patients in Uganda.

Assessment of the accuracy of malaria microscopy in private health facilities in Entebbe Municipality, Uganda: a cross-sectional study.

BACKGROUND: Although microscopy remains the gold standard for malaria diagnosis, little is known about its accuracy in the private health facilities in Uganda. This study evaluated the accuracy of malaria microscopy, and factors associated with inaccurate smear results at private health facilities in Entebbe Municipality, Uganda. METHODS: Between April and May 2018, all patients referred for a malaria smear in 16 private health facilities in Entebbe municipality were screened, and 321 patients were enrolled. A questionnaire was administered to collect demographic and clinical information, facility-based smear results were recorded from the participant's consultation notes, and a research slide was obtained for expert microscopy during exit interview. A health facility assessment was conducted, and information on experience in performing malaria microscopy was collected from all facility personnel reading smears and the data was linked to the participant's clinic visit. RESULTS: The test positivity rate of malaria parasitaemia was 15.0% by expert microscopy. The sensitivity, specificity and negative predictive value of the facility-based microscopy were high (95.8%, 90.1 and 99.2%, respectively). However; the positive predictive value (PPV) was low with 27/73 (63%) patients diagnosed with malaria not having the disease. Majority of the inaccurate results were from 2 of the 23 laboratory personnel reading the smears. The factors associated with inaccurate smear readings included being read by a technician; (1) who had less than 5 years' experience in reading malaria smears (adjusted Odds Ratio [aOR] = 9.74, 95% confidence interval [CI] (1.06-89.5), p-value = 0.04), and (2) who was examining less than 5 smears a day (aOR = 38.8, 95% CI 9.65-156, p-value < 0.001). CONCLUSIONS: The accuracy of malaria microscopy in this setting was high, although one third of the patients diagnosed with malaria did not have the disease. Majority of the errors in smear readings were made by two laboratory personnel, with the main factor associated with inaccurate smear results being low experience in malaria microscopy. In-service training may be sufficient to eliminate inaccurate smear results in this setting, and these private facilities would be ideal model facilities to improve the quality of malaria microscopy in Uganda especially in the public sector where accuracy is still poor.

Genetic diversity and genetic relatedness in Plasmodium falciparum parasite population in individuals with uncomplicated malaria based on microsatellite typing in Eastern and Western regions of Uganda, 2019-2020.

BACKGROUND: Genetic diversity and parasite relatedness are essential parameters for assessing impact of interventions and understanding transmission dynamics of malaria parasites, however data on its status in Plasmodium falciparum populations in Uganda is limited. Microsatellite markers and DNA sequencing were used to determine diversity and molecular characterization of P. falciparum parasite populations in Uganda. METHODS: A total of 147 P. falciparum genomic DNA samples collected from cross-sectional surveys in symptomatic individuals of 2-10 years were characterized by genotyping of seven highly polymorphic neutral microsatellite markers (n = 85) and genetic sequencing of the Histidine Rich Protein 2 (pfhrp2) gene (n = 62). ArcGIS was used to map the geographical distribution of isolates while statistical testing was done using Student's t-test or Wilcoxon's rank-sum test and Fisher's exact test as appropriate at P ≤ 0.05. RESULTS: Overall, 75.5% (95% CI 61.1-85.8) and 24.5% (95% CI14.2-38.9) of parasites examined were of multiclonal (mixed genotype) and single clone infections, respectively. Multiclonal infections occurred more frequently in the Eastern region 73.7% (95% CI 48.8-89.1), P < 0.05. Overall, multiplicity of infection (MOI) was 1.9 (95% CI 1.7-2.1), P = 0.01 that was similar between age groups (1.8 vs 1.9), P = 0.60 and regions (1.9 vs 1.8), P = 0.43 for the < 5 and ≥ 5 years and Eastern and Western regions, respectively. Genomic sequencing of the pfhrp2 exon2 revealed a high level of genetic diversity reflected in 96.8% (60/62) unique sequence types. Repeat type AHHAAAHHATD and HRP2 sequence Type C were more frequent in RDT-/PCR + samples (1.9% vs 1.5%) and (13% vs 8%), P < 0.05 respectively. Genetic relatedness analysis revealed small clusters of gene deleted parasites in Uganda, but no clustering with Eritrean parasites. CONCLUSION: High level of genetic diversity of P. falciparum parasites reflected in the frequency of multiclonal infections, multiplicity of infection and variability of the pfhrp2 gene observed in this study is consistent with the high malaria transmission intensity in these settings. Parasite genetic analysis suggested spontaneous emergence and clonal expansion of pfhrp2 deleted parasites that require close monitoring to inform national malaria diagnosis and case management policies.

The burden of drug resistant tuberculosis in a predominantly nomadic population in Uganda: a mixed methods study.

BACKGROUND: Emergence of drug resistant tuberculosis (DR-TB) has aggravated the tuberculosis (TB) public health burden worldwide and especially in low income settings. We present findings from a predominantly nomadic population in Karamoja, Uganda with a high-TB burden (3500 new cases annually) and sought to determine the prevalence, patterns, factors associated with DR-TB. METHODS: We used mixed methods of data collection. We enrolled 6890 participants who were treated for tuberculosis in a programmatic setting between January 2015 and April 2018. A cross sectional study and a matched case control study with conditional logistic regression and robust standard errors respectively were used to the determine prevalence and factors associated with DR-TB. The qualitative methods included focus group discussions, in-depth interviews and key informant interviews. RESULTS: The overall prevalence of DR-TB was 41/6890 (0.6%) with 4/64,197 (0.1%) among the new and 37/2693 (1.4%) among the previously treated TB patients respectively. The drug resistance patterns observed in the region were mainly rifampicin mono resistant (68.3%) and Multi Drug-Resistant Tuberculosis (31.7%). Factors independently associated with DR-TB were previous TB treatment, adjusted odds ratio (aOR) 13.070 (95%CI 1.552-110.135) and drug stock-outs aOR 0.027 (95%CI 0.002-0.364). The nomadic lifestyle, substance use, congested homesteads and poor health worker attitudes were a great challenge to effective treatment of TB. CONCLUSION: Despite having the highest national TB incidence, Karamoja still has a low DR-TB prevalence. Previous TB treatment and drug stock outs were associated with DR-TB. Regular supply of anti TB medications and health education may help to stem the burden of TB disease in this nomadic population.

Factors associated with concurrent wasting and stunting among children 6-59 months in Karamoja, Uganda.

Children with concurrent wasting and stunting (WaSt) and children with severe wasting have a similar risk of death. Existing evidence shows that wasting and stunting share similar causal pathways, but evidence on correlates of WaSt remains limited. Research on correlates of WaSt is needed to inform prevention strategies. We investigated the factors associated with WaSt in children 6-59 months in Karamoja Region, Uganda. We examined data for 33,054 children aged 6-59 months using June 2015 to July 2018 Food Security and Nutrition Assessment in Karamoja. We defined WaSt as being concurrently wasted (weight-for-height z-scores <-2.0) and stunted (height-for-age z-score <-2.0). We conducted multivariate mixed-effect logistic regression to assess factors associated with WaSt. Statistical significance was set at p < 0.05. In multivariate analysis, being male (adjusted odds ratio [aOR] = 1.79; 95% confidence interval [CI] [1.60-2.00]), aged 12-23 months (aOR = 2.25; 95% CI [1.85-2.74]), 36-47 months (aOR = 0.65; 95% CI [0.50-0.84]) and 48-59 months (aOR = 0.71; 95% CI [0.54-0.93]) were associated with WaSt. In addition, acute respiratory infection (aOR = 1.30; 95% CI [1.15-1.48]), diarrhoea (aOR = 1.25; 95% CI [1.06-1.48]) and malaria/fever (aOR = 0.83; 95% CI [0.73-0.96]) episodes were associated with WaSt. WaSt was significantly associated with maternal underweight (body mass index <18.5 kg/m2 ), short stature (height <160 cm), low mid-upper arm circumference (MUAC <23 cm) and having ≥4 live-births. WaSt was prevalent in households without livestock (aOR = 1.30; 95% CI [1.13-1.59]). Preventing the occurrence of WaSt through pragmatic and joint approaches are recommended. Future prospective studies on risk factors of WaSt to inform effective prevention strategies are recommended.

Blackwater Fever in Ugandan Children With Severe Anemia is Associated With Poor Postdischarge Outcomes: A Prospective Cohort Study.

BACKGROUND: Blackwater fever (BWF), one of the complications of severe malaria, has recently re-emerged as a cause of severe anemia (SA) in African children. However, postdischarge morbidity in children with BWF has previously not been described. METHODS: This was a descriptive cohort study in which children, aged 0-5 years, admitted to Jinja Regional Referral Hospital with acute episodes of SA (hemoglobin ≤5.0 g/dL) were followed up for 6 months after hospitalization. Incidence of readmissions or deaths during the follow-up period was compared between SA children with BWF and those without BWF. RESULTS: A total of 279 children with SA including those with BWF (n = 92) and no BWF (n = 187) were followed for the duration of the study. Overall, 128 (45.9%) of the study participants were readmitted at least once while 22 (7.9%) died during the follow-up period. After adjusting for age, sex, nutritional status, and parasitemia, SA children with BWF had higher risk of readmissions (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.1-2.5) and a greater risk of death (HR. 3.37; 95% CI, 1.3-8.5) compared with those without BWF. Malaria and recurrence of SA were the most common reasons for readmissions. CONCLUSIONS: There is a high rate of readmissions and deaths in the immediate 6 months after initial hospitalization among SA children in the Jinja hospital. SA children with BWF had increased risk of readmissions and deaths in the postdischarge period. Postdischarge malaria chemoprophylaxis should be considered for SA children living in malaria endemic areas.

The clinical spectrum of severe childhood malaria in Eastern Uganda.

BACKGROUND: Few recent descriptions of severe childhood malaria have been published from high-transmission regions. In the current study, the clinical epidemiology of severe malaria in Mbale, Eastern Uganda, is described, where the entomological inoculation rate exceeds 100 infective bites per year. METHODS: A prospective descriptive study was conducted to determine the prevalence, clinical spectrum and outcome of severe Plasmodium falciparum malaria at Mbale Regional Referral Hospital in Eastern Uganda. All children aged 2 months-12 years who presented on Mondays to Fridays between 8.00 am and 5.00 pm from 5th May 2011 until 30th April 2012 were screened for parasitaemia. Clinical and laboratory data were then collected from all P. falciparum positive children with features of WHO-defined severe malaria by use of a standardized proforma. RESULTS: A total of 10 208 children were screened of which 6582 (64%) had a positive blood film. Of these children, 662 (10%) had clinical features of severe malaria and were consented for the current study. Respiratory distress was the most common severity feature (554; 83.7%), while 365/585 (62.4%) had hyperparasitaemia, 177/662 (26.7%) had clinical jaundice, 169 (25.5%) had severe anaemia, 134/660 (20.2%) had hyperlactataemia (lactate ≥ 5 mmol/L), 93 (14.0%) had passed dark red or black urine, 52 (7.9%) had impaired consciousness and 49/662 (7.4%) had hypoxaemia (oxygen saturations < 90%). In-hospital mortality was 63/662 (9.5%) overall but was higher in children with either cerebral malaria (33.3%) or severe anaemia (19.5%). Factors that were independently associated with mortality on multivariate analysis included severe anaemia [odds ratio (OR) 5.36; 2.16-1.32; P = 0.0002], hyperlactataemia (OR 3.66; 1.72-7.80; P = 0.001), hypoxaemia (OR) 3.64 (95% CI 1.39-9.52; P = 0.008), and hepatomegaly (OR 2.29; 1.29-4.06; P = 0.004). No independent association was found between mortality and either coma or hyperparasitaemia. CONCLUSIONS: Severe childhood malaria remains common in Eastern Uganda where it continues to be associated with high mortality. An unusually high proportion of children with severe malaria had jaundice or gave a history of having recently passed dark red or black urine, an issue worthy of further investigation.

Molecular surveillance reveals the presence of pfhrp2 and pfhrp3 gene deletions in Plasmodium falciparum parasite populations in Uganda, 2017-2019.

BACKGROUND: Histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) are the only RDTs recommended for malaria diagnosis in Uganda. However, the emergence of Plasmodium falciparum histidine rich protein 2 and 3 (pfhrp2 and pfhrp3) gene deletions threatens their usefulness as malaria diagnostic and surveillance tools. The pfhrp2 and pfhrp3 gene deletions surveillance was conducted in P. falciparum parasite populations in Uganda. METHODS: Three-hundred (n = 300) P. falciparum isolates collected from cross-sectional malaria surveys in symptomatic individuals in 48 districts of eastern and western Uganda were analysed for the presence of pfhrp2 and pfhrp3 genes. Presence of parasite DNA was confirmed by PCR amplification of the 18s rRNA gene, msp1 and msp2 single copy genes. Presence or absence of deletions was confirmed by amplification of exon1 and exon2 of pfhrp2 and pfhrp3 using gene specific PCR. RESULTS: Overall, pfhrp2 and pfhrp3 gene deletions were detected in 29/300 (9.7%, 95% CI 6.6-13.6%) parasite isolates. The pfhrp2 gene was deleted in 10/300 (3.3%, 95% CI 1.6-6.0%) isolates, pfhrp3 in 9/300 (3.0%, 95% CI 1.4-5.6%) while both pfhrp2 and pfhrp3 were deleted in 10/300 (3.3%, 95% CI 1.6-6.0%) parasite isolates. Proportion of pfhrp2/3 deletions was higher in the eastern 14.7% (95% CI 9.7-20.0%) compared to the western region 3.1% (95% CI 0.8-7.7%), p = 0.001. Geographical location was associated with gene deletions aOR 6.25 (2.02-23.55), p = 0.003. CONCLUSIONS: This is the first large-scale survey reporting the presence of pfhrp2/3 gene deletions in P. falciparum isolates in Uganda. Roll out of RDTs for malaria diagnosis should take into consideration the existence of pfhrp2/3 gene deletions particularly in areas where they were detected. Periodic pfhrp2/3 surveys are recommended to inform future decisions for deployment of alternative RDTs.

Concurrently wasted and stunted children 6-59 months in Karamoja, Uganda: prevalence and case detection.

We assessed prevalence of concurrently wasted and stunted (WaSt) and explored the overlaps between wasted, stunted, underweight and low mid-upper arm circumference (MUAC) among children aged 6-59 months in Karamoja, Uganda. We also determined optimal weight-for-age (WAZ) and MUAC thresholds for detecting WaSt. We conducted secondary data analysis with 2015-2018 Food Security and Nutrition Assessment (FSNA) cross-sectional survey datasets from Karamoja. Wasting, stunting and underweight were defined as <-2.0 z-scores using WHO growth standards. Low MUAC was defined as <12.5 cm. We defined WaSt as concurrent wasting and stunting. Prevalence of WaSt was 4.96% (95% CI [4.64, 5.29]). WaSt was more prevalent in lean than harvest season (5.21% vs. 4.53%; p = .018). About half (53.92%) of WaSt children had low MUAC, and all were underweight. Younger children aged <36 months had more WaSt, particularly males. Males with WaSt had higher median MUAC than females (12.50 vs. 12.10 cm; p < .001). A WAZ <-2.60 threshold detected WaSt with excellent sensitivity (99.02%) and high specificity (90.71%). MUAC threshold <13.20 cm had good sensitivity (81.58%) and moderate specificity (76.15%) to detect WaSt. WaSt prevalence of 5% is a public health concern, given its high mortality risk. All children with WaSt were underweight and half had low MUAC. WAZ and MUAC could be useful tools for detecting WaSt. Prevalence monitoring and prospective studies on WAZ and MUAC cut-offs for WaSt detection are recommended. Future consideration to integrate WAZ into therapeutic feeding programmes is recommended to detect and treat WaSt children.

Systematic review of the status of pfhrp2 and pfhrp3 gene deletion, approaches and methods used for its estimation and reporting in Plasmodium falciparum populations in Africa: review of published studies 2010-2019.

BACKGROUND: Malaria rapid diagnostic tests based on histidine-rich protein-2 have played a vital role in improving malaria case management and surveillance particularly in Africa, where Plasmodium falciparum is predominant. However, their usefulness has been threatened by the emergence of gene deletion on P. falciparum histidine rich protein 2 (pfhrp2) and P. falciparum histidine rich protein 3 (pfhrp3). Use of standard and recommended methods is key for accurate investigation, confirmation and reporting of pfhrp2 and pfhrp3 gene deletion. METHODS: A systematic review was conducted to assess the status, methods and approaches that have been used for investigation, confirmation and reporting of pfhrp2 and pfhrp3 gene deletion in Africa. An online search was done using PubMed and MEDLINE Google Scholar for all articles published in English on pfhrp2/3 gene deletion in Africa. Relevant articles that met the inclusion criteria were summarized and assessed based on the protocol recommended by the World Health Organization for confirmation and reporting of pfhrp2/3 gene deletion. RESULTS: The search identified a total of 18 articles out of which 14 (77.7%) fulfilled the criteria for inclusion and were retained for review. The articles were distributed across 12 countries where the pfhrp2 and pfhrp3 gene deletion studies were conducted and reported. The level of pfhrp2/3 gene deletion across selected studies in Africa ranged from the highest 62% to the lowest 0.4%. There was wide variation in methods and approaches including study designs, size and sampling and whether both pfhrp2 and pfhrp3 double deletions or pfhrp2 single deletion were investigated, with a wide variation in laboratory methods. CONCLUSION: Based on the review, there is evidence of the presence of pfhrp2/3 gene-deleted P. falciparum parasites in Africa. The approaches and methods used for investigation, confirmation and reporting of pfhrp2/3 deleted parasites have varied between studies and across countries. Countries that are considering plans to investigate, confirm and report pfhrp2/3 deletion should use recommended standard and harmonized methods to prevent unnecessary recommendations for costly switch of RDTs in Africa.

Loss to follow-up and associated factors among adult people living with HIV at public health facilities in Wakiso district, Uganda: a retrospective cohort study.

BACKGROUND: Loss to follow-up (LTFU) from care among people living with HIV (PLHIV) is thought to be more common in the public setting compared to the private health care. It is anticipated that the problem may become worse with the current "test and treat" policy in Uganda due to the likely increases in patient loads and its attendant pressure on health care providers to support patient counseling. This study determined the incidence and factors associated with LTFU from HIV care among adult PLHIV in public health facilities in Wakiso district, Uganda. METHODS: This was a retrospective cohort study that involved the review of 646 records of patients initiated on antiretroviral therapy (ART) between January 1st, 2015 and December 31st, 2017 at 13 randomly selected public health facilities in Wakiso district. The cox proportional hazards regression was used to determine the factors associated with LTFU. The results were supported by sequential in-depth and key informant interviews to explore reasons for LTFU. RESULTS: Of the 646 patients enrolled, 391 were female (60.5%), 282 were below 30 years (43.6%) and 207 were married (50.1%). A total of 216 patients (33.4%) had no documented outcomes and were considered LTFU. The incidence of LTFU was 21 per 1000 person months (95% confidence interval (CI): 18-25 per 1000 person months). Factors associated with LTFU included having normal weight compared to underweight (adjusted hazard ratio (aHR) 0.64, 95% CI: 0.45-0.90, p = 0.011), receiving HIV care from hospitals compared to lower level facilities (aHR 0.22, 95% CI: 0.12-0.41, p < 0.001), and no telephone contact compared to those with a telephone contact (aHR 2.16, 95% CI: 1.33-3.51, p = 0.002). Stigmatization and long waiting times were the prominent reasons for LTFU reported from the in-depth and key informant interviews. CONCLUSIONS: The incidence of LTFU in public health facilities in Uganda is quite high and is associated with being underweight, not having a telephone contact to receive reminders and receiving care at lower level facilities. Early diagnosis, routine use of patient address locator forms and improved quality of HIV care at lower level health facilities may reduce LTFU among PLHIV.

Caregiver responses and association with delayed care-seeking in children with uncomplicated and severe malaria.

BACKGROUND: Gaps remain in understanding the role of caregiver responses on time to seek appropriate care. The objective of this study was to describe caregiver responses to illness and the impact of these responses on time to seek appropriate care among children with malaria. METHODS: A case-control study of 325 children with severe (cases) and 325 children with uncomplicated (controls) malaria was conducted in Jinja, Uganda. Caregivers' responses to their children's illnesses and time to seek appropriate care were documented. Responses included staying at home, seeking care at drug shops, and seeking care at public health facilities classified into two types: (1) health facilities where caregiver initially sought care before enrollment, and (2) health facilities where children were provided appropriate care and enrolled in the study. Weighted Cox regression was used to determine risk factors for delays in time to seek appropriate care within 24 h of illness onset. RESULTS: Children staying home on self-medication was the most common initial response to illness among caregivers of controls (57.5%) and cases (42.4%, p < 0.001), followed by staying at home without medication (25.2%) and seeking care at drug shops (32.0%) for caregivers of controls and cases, respectively. Seeking care at drug shops was more common among caregivers of cases than of controls (32.0% vs. 12.3%; p < 0.001). However, compared to public health facilities, drug shops offered sub-optimal services with children less likely to have been examined (50.0% vs. 82.9%; p < 0.001) or referred to another facility (12.5% vs. 61.4%; p < 0.001). Upon adjustment for known risk factors for delay, initially seeking care at a drug shop (HR 0.37, p = 0.036) was associated with delay in seeking care at a health facility where appropriate care was provided. In contrast, those initially seeking care at public health facility before enrollment were more likely to subsequently seek care at another public health facility where appropriate care was provided (HR 5.55, p < 0.001). CONCLUSION: Caregivers should be educated on the importance of promptly seeking care at a health facility where appropriate care can be provided. The role of drug shops in providing appropriate care to children with malaria needs to be reviewed.

Measurement error of mean sac diameter and crown-rump length among pregnant women at Mulago hospital, Uganda.

BACKGROUND: Ultrasonography is essential in the prenatal diagnosis and care for the pregnant mothers. However, the measurements obtained often contain a small percentage of unavoidable error that may have serious clinical implications if substantial. We therefore evaluated the level of intra and inter-observer error in measuring mean sac diameter (MSD) and crown-rump length (CRL) in women between 6 and 10 weeks' gestation at Mulago hospital. METHODS: This was a cross-sectional study conducted from January to March 2016. We enrolled 56 women with an intrauterine single viable embryo. The women were scanned using a transvaginal (TVS) technique by two observers who were blinded of each other's measurements. Each observer measured the CRL twice and the MSD once for each woman. Intra-class correlation coefficients (ICCs), 95% limits of agreement (LOA) and technical error of measurement (TEM) were used for analysis. RESULTS: Intra-observer ICCs for CRL measurements were 0.995 and 0.993 while inter-observer ICCs were 0.988 for CRL and 0.955 for MSD measurements. Intra-observer 95% LOA for CRL were ± 2.04 mm and ± 1.66 mm. Inter-observer LOA were ± 2.35 mm for CRL and ± 4.87 mm for MSD. The intra-observer relative TEM for CRL were 4.62% and 3.70% whereas inter-observer relative TEM were 5.88% and 5.93% for CRL and MSD respectively. CONCLUSIONS: Intra- and inter-observer error of CRL and MSD measurements among pregnant women at Mulago hospital were acceptable. This implies that at Mulago hospital, the error in pregnancy dating is within acceptable margins of ±3 days in first trimester, and the CRL and MSD cut offs of ≥7 mm and ≥ 25 mm respectively are fit for diagnosis of miscarriage on TVS. These findings should be extrapolated to the whole country with caution. Sonographers can achieve acceptable and comparable diagnostic accuracy levels of MSD and CLR measurements with proper training and adherence to practice guidelines.

Burden and factors associated with clinical neonatal sepsis in urban Uganda: a community cohort study.

BACKGROUND: Neonatal sepsis is one of the most important causes of mortality in developing countries and yet the most preventable. In developing countries clinical algorithms are used to diagnose clinical neonatal sepsis because of inadequate microbiological services. Most information on incidence and risk factors of neonatal sepsis are from hospital studies which may not be generalized to communities where a significant proportion of mothers do not deliver from health facilities. This study, conducted in urban Uganda, sought to determine the community based incidence of clinical neonatal sepsis and the factors associated. METHODS: This was a cohort of mother-neonate pairs in Kampala, Uganda from March to May 2012. The enrolled neonates were assessed for clinical sepsis and factors associated, and followed up till the end of the neonatal period. STATA version 10 was used to analyse the data. RESULTS: The community based incidence of neonatal sepsis was 11% (95% CI: 7.6-14.4). On bivariate analysis, lack of financial support from the father (OR 4.09, 95% CI 1.60-10.39) and prolonged rupture of membranes more than 18 h prior to delivery (OR 11.7, 95% CI 4.0-31.83) were significantly associated with neonatal sepsis. Maternal hand washing prior to handling the baby was found to be protective of neonatal sepsis (OR 0.41, 95% CI 0.18-0.94). Of the 317 infants who completed the follow up period, one died within the neonatal period giving a neonatal mortality of 0.003%. CONCLUSION: The high incidence of clinical neonatal sepsis in this urban community with high rates of antenatal care attendance and health facility delivery places a demand on the need to improve the quality of antenatal, perinatal and postnatal care in health facilities with regards to infection prevention including promoting simple practices like hand washing. The astoundingly low mortality rate is most likely because this was a low risk cohort. However it may also suggest that the neonatal mortality in developing countries may be reduced with promotion of simple low cost interventions like community follow up of neonates using village health teams or domiciliary care.

High rate of inappropriate blood transfusions in the management of children with severe anemia in Ugandan hospitals.

BACKGROUND: Severe anaemia (SA) is a common reason for hospitalisation of children in sub-Saharan Africa but the extent to which blood transfusion is used appropriately in the management of severe anemia has hitherto remained unknown. We report on the use of blood transfusion in the management of anemic children in two hospitals in Uganda. METHODS: Inpatient records of children 0-5 years of age admitted to Lira and Jinja regional referral hospitals in Uganda were reviewed for children admitted on selected days between June 2016 and May 2017. Data was extracted on the results, if any, of pre-transfusion hemoglobin (Hb) level, whether or not a blood transfusion was given and inpatient outcome for all children with a diagnosis of 'severe anemia'. Qualitative data was also collected from health workers to explain the reasons for the clinical practices at the two hospitals. RESULTS: Overall, 574/2275 (25.2%) of the children admitted in the two hospitals were assigned a diagnosis of SA. However 551 (95.9%) of children assigned a diagnosis of SA received a blood transfusion, accounting for 551/560 (98.4%) of the blood transfusions in the pediatric wards. Of the blood transfusions in SA children, only 245 (44.5%) was given appropriately per criteria (Pre-transfusion Hb ≤ 6 g/dL), while 306 (55.5%) was given inappropriately; (pre-transfusion Hb not done, n = 216, or when a transfusion is not indicated [Hb > 6.0 g/dl], n = 90). SA children transfused appropriately per Hb criteria had lower inpatient mortality compared to those transfused inappropriately, (7 (2.9%) vs. 22 (7.2%), [OR 0.4, 95% CI 0.16, 0.90]). Major issues identified by health workers as affecting use of blood transfusion included late presentation of SA children to hospital and unreliable availability of equipment for measurement of Hb. CONCLUSION: More than half the blood transfusions given in the management of anemic children admitted to Lira and Jinja hospitals was given inappropriately either without pre-transfusion Hb testing or when not indicated. Verification of Hb level by laboratory testing and training of health workers to adhere to transfusion guidelines could result in a substantial decrease in inappropriate blood transfusion in Ugandan hospitals.

Risk factors, person, place and time characteristics associated with Hepatitis E Virus outbreak in Napak District, Uganda.

BACKGROUND: Hepatitis E is self-limiting, but can cause death in most at risk groups like pregnant women and those with preexisting acute liver disease. In developing countries it presents as epidemic, in 2014 Hepatitis E Virus (HEV) outbreak was reported in Napak district Uganda. The role of factors in this setting that might have propagated this HEV epidemic, including host, agent, and environmental characteristics, were still not clear. This study was therefore conducted to investigate the risk factors, person, place and time characteristics, associated with the hepatitis E virus (HEV) epidemic in Napak district. METHODS: Review of line lists data for epidemiological description and matched case control study on neighborhood and age in the ratio of 1:2 were used to assess risk factors for HEV outbreak in Napak. Cluster and random sampling were used to obtain a sample size of 332, (111 cases, 221 controls). Possible interaction and confounding was assessed using conditional logistic regression. RESULTS: Over 1359 cases and 30 deaths were reported during 2013/2014 HEV outbreak. The mean age of patients was 29 ± years, 57.9% of cases were females. Overall case Fatality Ratio was 2.2% in general population but 65.2% in pregnant women. More than 94% of the cases were reported in the sub counties of Napak, 5.7% of cases were reported in the outside neighboring districts. The epidemic peaked in January 2014 and gradually subsided by December 2014. Risk factors found to be associated with HEV included drinking untreated water (OR 6.69, 95% CI 3.15-14.16), eating roadside food (OR 6.11, 95% CI 2.85-13.09), reported not cleaning utensils (OR 3.24, 95% CI 1.55-1.76), and being a hunter (OR 1.14, 95% CI 1.03-12.66). CONCLUSION: The results of this study suggest that the virus is transmitted by the feco-oral route through contaminated water. They also suggest that active surveillance and appropriate measures targeting community and routine individual health actions are important to prevent transmission and decrease the deaths.