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.

LLIN Evaluation in Uganda Project (LLINEUP2)-Factors associated with coverage and use of long­lasting insecticidal nets following the 2020-21 national mass distribution campaign: a cross-sectional survey of 12 districts.

BACKGROUND: In 2020-2021, long-lasting insecticidal nets (LLINs) were distributed nationwide in Uganda during the COVID-19 pandemic. A cross-sectional survey was conducted in 12 districts to evaluate the impact of the campaign 1-5 months after LLIN distribution. METHODS: During April-May 2021, households were randomly selected from target areas (1-7 villages) surrounding 12 government-run health facilities established as Malaria Reference Centres; at least 50 households were enrolled per cluster. Outcomes included household ownership of LLINs distributed through the universal coverage campaign (UCC) (at least one UCC LLIN), adequate coverage of UCC LLINs (at least one UCC LLIN per 2 residents), and use of LLINs (resident slept under a LLIN the previous night). Multivariate logistic regression models were used to identify household- and individual-level factors associated with outcomes, controlling for clustering around health facilities. RESULTS: In total, 634 households, with 3342 residents and 1631 bed-nets, were included. Most households (93.4%) owned at least 1 UCC LLIN, but only 56.8% were adequately covered by UCC LLINs. In an adjusted analysis, the factor most strongly associated with adequate coverage by UCC LLINs was fewer household residents (1-4 vs 7-14; adjusted odds ratio [aOR] 12.96, 95% CI 4.76-35.26, p < 0.001; 5-6 vs 7-14 residents; aOR 2.99, 95% CI 1.21-7.42, p = 0.018). Of the 3166 residents of households that owned at least one UCC LLIN, only 1684 (53.2%) lived in adequately covered households; 89.9% of these used an LLIN the previous night, compared to 1034 (69.8%) of 1482 residents living in inadequately covered households. In an adjusted analysis, restricted to residents of inadequately covered households, LLIN use was higher in children under-five than those aged 5-15 years (aOR 3.04, 95% CI 2.08-4.46, p < 0.001), and higher in household heads than distantly-related residents (aOR 3.94, 95% CI 2.38-6.51, p < 0.001). CONCLUSIONS: Uganda's 2021-21 campaign was successful, despite the COVID-19 pandemic. In future campaigns, strategies should be adopted to ensure high LLIN coverage, particularly for larger households. A better understanding of the drivers of LLIN use within households is needed to guide future interventions, educational messages, and behaviour change communication strategies; school-aged children and distantly-related residents appear vulnerable and could be targeted.

Gender difference in the incidence of malaria diagnosed at public health facilities in Uganda.

BACKGROUND: Routine malaria surveillance data in Africa primarily come from public health facilities reporting to national health management information systems. Although information on gender is routinely collected from patients presenting to these health facilities, stratification of malaria surveillance data by gender is rarely done. This study evaluated gender difference among patients diagnosed with parasitological confirmed malaria at public health facilities in Uganda. METHODS: This study utilized individual level patient data collected from January 2020 through April 2021 at 12 public health facilities in Uganda and cross-sectional surveys conducted in target areas around these facilities in April 2021. Associations between gender and the incidence of malaria and non-malarial visits captured at the health facilities from patients residing within the target areas were estimated using poisson regression models controlling for seasonality. Associations between gender and data on health-seeking behaviour from the cross-sectional surveys were estimated using poisson regression models controlling for seasonality. RESULTS: Overall, incidence of malaria diagnosed per 1000 person years was 735 among females and 449 among males (IRR = 1.72, 95% CI 1.68-1.77, p < 0.001), with larger differences among those 15-39 years (IRR = 2.46, 95% CI 2.34-2.58, p < 0.001) and over 39 years (IRR = 2.26, 95% CI 2.05-2.50, p < 0.001) compared to those under 15 years (IRR = 1.46, 95% CI 1.41-1.50, p < 0.001). Female gender was also associated with a higher incidence of visits where malaria was not suspected (IRR = 1.77, 95% CI 1.71-1.83, p < 0.001), with a similar pattern across age strata. These associations were consistent across the 12 individual health centres. From the cross-sectional surveys, females were more likely than males to report fever in the past 2 weeks and seek care at the local health centre (7.5% vs. 4.7%, p = 0.001) with these associations significant for those 15-39 years (RR = 2.49, 95% CI 1.17-5.31, p = 0.018) and over 39 years (RR = 2.56, 95% CI 1.00-6.54, p = 0.049). CONCLUSIONS: Females disproportionately contribute to the burden of malaria diagnosed at public health facilities in Uganda, especially once they reach childbearing age. Contributing factors included more frequent visits to these facilities independent of malaria and a higher reported risk of seeking care at these facilities for febrile illnesses.

Associations between environmental covariates and temporal changes in malaria incidence in high transmission settings of Uganda: a distributed lag nonlinear analysis.

BACKGROUND: Environmental factors such as temperature, rainfall, and vegetation cover play a critical role in malaria transmission. However, quantifying the relationships between environmental factors and measures of disease burden relevant for public health can be complex as effects are often non-linear and subject to temporal lags between when changes in environmental factors lead to changes in malaria incidence. The study investigated the effect of environmental covariates on malaria incidence in high transmission settings of Uganda. METHODS: This study leveraged data from seven malaria reference centres (MRCs) located in high transmission settings of Uganda over a 24-month period. Estimates of monthly malaria incidence (MI) were derived from MRCs' catchment areas. Environmental data including monthly temperature, rainfall, and normalized difference vegetation index (NDVI) were obtained from remote sensing sources. A distributed lag nonlinear model was used to investigate the effect of environmental covariates on malaria incidence. RESULTS: Overall, the median (range) monthly temperature was 30 °C (26-47), rainfall 133.0 mm (3.0-247), NDVI 0.66 (0.24-0.80) and MI was 790 per 1000 person-years (73-3973). Temperature of 35 °C was significantly associated with malaria incidence compared to the median observed temperature (30 °C) at month lag 2 (IRR: 2.00, 95% CI: 1.42-2.83) and the increased cumulative IRR of malaria at month lags 1-4, with the highest cumulative IRR of 8.16 (95% CI: 3.41-20.26) at lag-month 4. Rainfall of 200 mm significantly increased IRR of malaria compared to the median observed rainfall (133 mm) at lag-month 0 (IRR: 1.24, 95% CI: 1.01-1.52) and the increased cumulative IRR of malaria at month lags 1-4, with the highest cumulative IRR of 1.99(95% CI: 1.22-2.27) at lag-month 4. Average NVDI of 0.72 significantly increased the cumulative IRR of malaria compared to the median observed NDVI (0.66) at month lags 2-4, with the highest cumulative IRR of 1.57(95% CI: 1.09-2.25) at lag-month 4. CONCLUSIONS: In high-malaria transmission settings, high values of environmental covariates were associated with increased cumulative IRR of malaria, with IRR peaks at variable lag times. The complex associations identified are valuable for designing strategies for early warning, prevention, and control of seasonal malaria surges and epidemics.

Staging of COVID-19 disease; using selected laboratory profiles for prediction, prevention and management of severe SARS-CoV-2 infection in Africa-review.

There are many uncertainties on the future management of the coronavirus disease 19 (COVID-19) in Africa. By July 2021, Africa had lagged behind the rest of the world in Covid-19 vaccines uptake, accounting for just 1.6% of doses administered globally. During that time COVID 19 was causing an average death rate of 2.6% in Africa, surpassing the then global average of 2.2%. There were no clear therapeutic guidelines, yet inappropriate and unnecessary treatments may have led to unwanted adverse events such as worsening of hyperglycemia and precipitating of ketoacidosis in administration of steroid therapy. in order to provide evidence-based policy guidelines, we examined peer-reviewed published articles in PubMed on COVID 19, or up-to date data, we focused our search on publications from 1st May 2020 to 15th July, 2021. For each of the studies, we extracted data on pathophysiology, selected clinical chemistry and immunological tests, clinical staging and treatment. Our review reports a gross unmet need for vaccination, inadequate laboratory capacity for immunological tests and the assessment of individual immune status, clinical staging and prediction of disease severity. We recommend selected laboratory tools in the assessment of individual immune status, prediction of disease severity and determination of the exact timing for suitable therapy, especially in individuals with co-morbidities.

Factors associated with utilization of insecticide-treated nets in children seeking health care at a Ugandan hospital: perspective of child caregivers.

In Uganda malaria causes more morbidity and mortality than any other disease and children below 5 years contribute the biggest percentage of malaria related mortality. Insecticide treated nets (ITNs) are currently one of the most cost effective option for reducing malaria-related morbidity and mortality, however the factors affecting their utilization in Uganda are still not well understood. This study examined the prevalence and factors associated with ITN utilization among children of age 0-12 years seeking health care from a Ugandan hospital using caregiver's reports. A cross sectional design was used to collect data using a semi-structured questionnaire from 418 participants. Binary logistic regression was employed to determine predictors of ITN utilization. Results show that the prevalence of ITN utilization among children seeking health care was 34.2%. ITN utilization was higher among children of age <5 years [37.0, 95% CI 31.81-42.21] as compared to children aged ≥5 years [22.9, 95% CI 13.77-32.01]. Source of mosquito net (OR = 13.53, 95% CI = 6.47-28.27), formal employment by head of household (OR = 6.00, 95% CI = 1.95-18.48), sharing a bed with parent (s) (OR = 2.61, 95% CI = 1.21-5.63) and number of children below 12 years in a household (OR = 0.80, 95% CI = 0.65-0.99), were significant predictors of utilization. ITN utilization among children was below the set national target. The predictors identified by this study reveal opportunities that can be taken advantage of by malaria control programs to achieve the desired rates of utilization and subsequently malaria prevention in children.

Contraceptive acceptability and associated factors among young women (15-24) living with HIV/AIDS: a hospital-based study in Kampala, Uganda.

Introduction: In Uganda, over 43% of all pregnancies among young women (15-24 years) living with HIV are either unwanted or mistimed. Unintended pregnancies account for 21.3% of neonatal HIV infections. The objective was to determine acceptability of contraceptives and associated factors among young women living with HIV attending HIV clinics in Kampala. Methods: Between February and May 2019, 450 young women attending public HIV clinics (Kisenyi HC IV, Kiswa HC III and Komamboga HC III) in Kampala were systematically enrolled in a cross sectional study and interviewed using structured questionnaires. We used modified Poisson regression to determine the factors associated with acceptability of contraceptive. Data were analyzed using STATA 13.0. Statistical significance was determined at a P values < 0.05. Results: Contraceptive acceptability was 40.7% (95% CI: 27.6%-53.6%). Older age group (20-24 years) (aPR; 2.42, 95%CI; 1.06-5.52, P = 0.035), age at sex debut ≥ 18 years (aPR;1.25,95%CI; 1.13-1.38, P<0.001), having friend on contraceptives (aPR; 1.90, 95%CI; 1.10 - 3.26; P =0.021) and being married (aPR; 1.20, 95%CI; 1.09 - 1.32, P<0.001) were significantly associated with acceptability of contraceptives. Conclusion: There is a low acceptability for contraceptives. Younger age group who are not yet married need to be targeted.

Prevalence and factors associated with depression symptoms among school-going adolescents in Central Uganda.

BACKGROUND: Depression in adolescents constitutes a global public health concern. However, data on its prevalence and associated factors are limited in low income countries like Uganda. METHODS: Using a cross-sectional descriptive study design, 519 adolescent students in 4 secondary schools in Mukono district, Uganda, were randomly selected after meeting study criteria. The 4 school types were: boarding mixed (boys and girls) school; day mixed school; girls' only boarding school; and, boys' only boarding school. The 519 participants filled out standardized questionnaires regarding their socio-demographic characteristics and health history. They were then screened for depression using the Children Depression Inventory (CDI) and those with a cut-off of 19 were administered the Mini International Neuro-Psychiatric Interview for Children and Adolescents 2.0 (MINI-KID), to ascertain the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM IV) diagnostic types of depression and any co morbidity. Logistic regression analyses were used to assess factors associated with significant depression symptoms (a score of 19 or more on the CDI). RESULTS: There were 301 (58 %) boys and 218 (42 %) girls with age range 14-16 years and a mean age of 16 years (SD 2.18). Of 519 participants screened with the CDI, 109 (21 %) had significant depression symptoms. Of the 109 participants with significant depression symptoms, only 74 were evaluated with the MINI-KID and of these, 8 (11 %) met criteria for major depression and 6 (8 %) met criteria for dysthymia. Therefore, among participants that were assessed with both the CDI and the MINI-KID (n = 484), the prevalence of depressive disorders was 2.9 %. In this sample, 15 (3.1 %) reported current suicidal ideation. In the logistic regression analyses, significant depression symptoms were associated with single-sex schools, loss of parents and alcohol consumption. LIMITATIONS: This is a cross-sectional study therefore, causal relationships are difficult to establish. Limited resources and the lack of collateral information precluded the assessment of a number of potential factors that could be associated with adolescent depression. The MINI-KID was administered to only 74 out of 109 students who scored ≥19 on the CDI since 35 students could not be traced again due to limited resources at the time. CONCLUSIONS: Significant depression symptoms are prevalent among school-going adolescents and may progress to full-blown depressive disorders. Culturally sensitive psychological interventions to prevent and treat depression among school-going adolescents are urgently needed.

Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda-a reflection of differences in policies regarding withdrawal of chloroquine?

BACKGROUND: Malaria is still a major public health problem in the world and sub-Saharan Africa is one of the most affected areas. Efforts to control malaria are highly affected by drug resistance to commonly used antimalarials. The introduction of artemisinin based combination therapy (ACT) as a first line drug seems to be a major step in treatment of uncomplicated malaria, though search for drugs to combine with artemisinins still continues. There have been reports on increased prevalence of the wild type markers Pfcrt 76K and Pfmdr1 86N in some African countries and ideas of using chloroquine (CQ) in intermittent presumptive treatment for adults (IPTa) is coming up. The common combination of artemether and lumefantrine even selects for parasites that are wild type at these positions. This study is comparing prevalence of mutation at these two positions in two East African countries with ACT as their first line drug but following somewhat different drug policies regarding CQ. In Tanzania CQ was stopped in 2001 but in Uganda CQ was retained in combination with sulfadoxine-pyrimethamine (SP) and used in home based management of fever for some time. SP is still used in IPT for pregnant women. METHODS: Blood smears and dried blood spots on Whatman filter papers were collected from 100 patients with uncomplicated malaria in Mwanza, Tanzania and 100 patients from Iganga, Uganda. DNA was extracted from all samples using Tris EDTA method. PCR and RFLP were performed and sequencing done on Pfcrt amplification products. RESULTS: The prevalence of K76T mutations at Pfcrt in samples from Mwanza, Tanzania was 40.5% (34/84) and 100% (100/100) in samples from Iganga, Uganda. Prevalence of N86Y mutations in Pfmdr1 was 16.9% (13/77) and 77.7% (63/81) in samples from Mwanza and Iganga, respectively. The re-emergence of CQ sensitive isolates in Mwanza, Tanzania showed the haplotype CVMNK typical for wild type isolates. CONCLUSIONS: The prevalence of CQ resistant parasites in Mwanza, Tanzania is low compared to the existing high level of resistant parasites in Iganga, Uganda. This could be an indication that CQ may become useful in the future in Tanzania. This study shows clearly that there is a difference in mutations at these positions in these two countries implementing similar but somewhat different drug policies. In Uganda the drug resistance has reached fixation while in Tanzania the prevalence is going down.