Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study

BACKGROUND: Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance. METHODS: An observational cohort of 49 symptomatic patients, diagnosed with uncomplicated P. falciparum malaria by rapid diagnostic test, had blood taken for malaria blood films and P. falciparum DNA polymerase chain reaction (PCR). Following diagnosis, patients were treated with artemether-lumefantrine (Coartem®) and invited to return to the health facility after 28 days for repeat blood film and PCR. All PCR P. falciparum positive samples were analysed for molecular markers of lumefantrine and chloroquine resistance. RESULTS: Of 49 patients recruited on the basis of a positive rapid diagnostic test, only 16 were confirmed to have P. falciparum by PCR. At follow-up, 14 were PCR-negative for malaria, one was lost to follow-up and one blood specimen had insufficient blood for a PCR analysis. All 16 with PCR-confirmed malaria carried a single copy of the multi-drug resistant (mdr1) gene, and the wild type asparagine allele mdr1 codon 86 (mdr1 86N). Ten of the 16 samples carried the wild type haplotype (CVMNK) at codons 72-76 of the chloroquine resistance transporter gene (pfcrt); three samples carried the resistant CVIET allele; one carried both the resistant and wild type, and in two samples the allele could not be analysed. CONCLUSIONS: The absence of mdr1 gene copy number variation detected in this study suggests lumefantrine resistance has yet to emerge in KwaZulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation

The impact of the COVID-19 lockdown on HIV care in 65 South African primary care clinics: an interrupted time series analysis.

BACKGROUND: The effect of the COVID-19 pandemic on HIV outcomes in low-income and middle-income countries is poorly described. We aimed to measure the impact of the 2020 national COVID-19 lockdown on HIV testing and treatment in KwaZulu-Natal, South Africa, where 1·7 million people are living with HIV. METHODS: In this interrupted time series analysis, we analysed anonymised programmatic data from 65 primary care clinics in KwaZulu-Natal province, South Africa. We included data from people testing for HIV, initiating antiretroviral therapy (ART), and collecting ART at participating clinics during the study period, with no age restrictions. We used descriptive statistics to summarise demographic and clinical data, and present crude summaries of the main outcomes of numbers of HIV tests per month, ART initiations per week, and ART collection visits per week, before and after the national lockdown that began on March 27, 2020. We used Poisson segmented regression models to estimate the immediate impact of the lockdown on these outcomes, as well as post-lockdown trends. FINDINGS: Between Jan 1, 2018, and July 31, 2020, we recorded 1 315 439 HIV tests. Between Jan 1, 2018, and June 15, 2020, we recorded 71 142 ART initiations and 2 319 992 ART collection visits. We recorded a median of 41 926 HIV tests per month before lockdown (January, 2018, to March, 2020; IQR 37 838-51 069) and a median of 38 911 HIV tests per month after lockdown (April, 2020, to July, 2020; IQR 32 699-42 756). In the Poisson regression model, taking into account long-term trends, lockdown was associated with an estimated 47·6% decrease in HIV testing in April, 2020 (incidence rate ratio [IRR] 0·524, 95% CI 0·446-0·615). ART initiations decreased from a median of 571 per week before lockdown (IQR 498-678), to 375 per week after lockdown (331-399), with an estimated 46·2% decrease in the Poisson regression model in the first week of lockdown (March 30, 2020, to April 5, 2020; IRR 0·538, 0·459-0·630). There was no marked change in the number of ART collection visits (median 18 519 visits per week before lockdown [IQR 17 074-19 922] vs 17 863 visits per week after lockdown [17 509-18 995]; estimated effect in the first week of lockdown IRR 0·932, 95% CI 0·794-1·093). As restrictions eased, HIV testing and ART initiations gradually improved towards pre-lockdown levels (slope change 1·183/month, 95% CI 1·113-1·256 for HIV testing; 1·156/month, 1·085-1·230 for ART initiations). INTERPRETATION: ART provision was generally maintained during the 2020 COVID-19 lockdown, but HIV testing and ART initiations were heavily impacted. Strategies to increase testing and treatment initiation should be implemented. FUNDING: Wellcome Trust, Africa Oxford Initiative

An assessment of nutritional status in children of rural, northern KwaZulu-Natal province

Background: Childhood malnutrition in South Africa is largely perceived as one of undernutrition, with the opposite end of the spectrum (overnutrition) being evidenced in the increasing prevalence of childhood obesity, demonstrated to be associated with chronic metabolic diseases in adulthood. Targeting childhood malnutrition is a potential interventional strategy to prevent non-communicable diseases amongst adults. As the prevalence of malnutrition (undernutrition and overnutrition) in rural, northern KwaZulu-Natal province, South Africa, is largely unknown, this study aimed to determine the baseline nutritional status of children attending primary healthcare facilities within the Bethesda Hospital catchment area.Methods: This quantitative, cross-sectional study included children aged 6 weeks to 19 years, attending any primary healthcare clinics for over a 3 months period. Anthropometric measurements were obtained to categorise the children according to the World Health Organisation’s (WHO) nutritional classifications.Results: Stunting in children aged less than 5 years was found to be lower (14%) than nationally representative studies (27%); however, 14.4% of the infants aged 6 weeks to 5 months were overweight, increasing to 32.3% in those aged 14–19 years. Males in the 6-weeks to 5-month age group were more likely to be overweight/obese and stunted than females in the same age group.Conclusion: Undernutrition is showing a downward trend, which is a testament to initiatives to reduce food insecurity amongst the poor. However, the emerging upward trend of overweight/obesity in children of all ages, indicates the need to have a national discussion on over- and undernutrition, its causes and implications

An assessment of nutritional status in children of rural, northern KwaZulu-Natal province

Background: Childhood malnutrition in South Africa is largely perceived as one of undernutrition, with the opposite end of the spectrum (overnutrition) being evidenced in the increasing prevalence of childhood obesity, demonstrated to be associated with chronic metabolic diseases in adulthood. Targeting childhood malnutrition is a potential interventional strategy to prevent non-communicable diseases amongst adults. As the prevalence of malnutrition (undernutrition and overnutrition) in rural, northern KwaZulu-Natal province, South Africa, is largely unknown, this study aimed to determine the baseline nutritional status of children attending primary healthcare facilities within the Bethesda Hospital catchment area.Methods: This quantitative, cross-sectional study included children aged 6 weeks to 19 years, attending any primary healthcare clinics for over a 3 months period. Anthropometric measurements were obtained to categorise the children according to the World Health Organisation’s (WHO) nutritional classifications.Results: Stunting in children aged less than 5 years was found to be lower (14%) than nationally representative studies (27%); however, 14.4% of the infants aged 6 weeks to 5 months were overweight, increasing to 32.3% in those aged 14–19 years. Males in the 6-weeks to 5-month age group were more likely to be overweight/obese and stunted than females in the same age group.Conclusion: Undernutrition is showing a downward trend, which is a testament to initiatives to reduce food insecurity amongst the poor. However, the emerging upward trend of overweight/obesity in children of all ages, indicates the need to have a national discussion on over- and undernutrition, its causes and implications.</jats:p

Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated <it>Plasmodium falciparum</it> malaria in northern KwaZulu-Natal: an observational cohort study

Abstract Background Recent malaria epidemics in KwaZulu-Natal indicate that effective anti-malarial therapy is essential for malaria control. Although artemether-lumefantrine has been used as first-line treatment for uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal since 2001, its efficacy has not been assessed since 2002. The objectives of this study were to quantify the proportion of patients treated for uncomplicated P. falciparum malaria with artemether-lumefantrine who failed treatment after 28 days, and to determine the prevalence of molecular markers associated with artemether-lumefantrine and chloroquine resistance. Methods An observational cohort of 49 symptomatic patients, diagnosed with uncomplicated P. falciparum malaria by rapid diagnostic test, had blood taken for malaria blood films and P. falciparum DNA polymerase chain reaction (PCR). Following diagnosis, patients were treated with artemether-lumefantrine (Coartem®) and invited to return to the health facility after 28 days for repeat blood film and PCR. All PCR P. falciparum positive samples were analysed for molecular markers of lumefantrine and chloroquine resistance. Results Of 49 patients recruited on the basis of a positive rapid diagnostic test, only 16 were confirmed to have P. falciparum by PCR. At follow-up, 14 were PCR-negative for malaria, one was lost to follow-up and one blood specimen had insufficient blood for a PCR analysis. All 16 with PCR-confirmed malaria carried a single copy of the multi-drug resistant (mdr1) gene, and the wild type asparagine allele mdr1 codon 86 (mdr1 86N). Ten of the 16 samples carried the wild type haplotype (CVMNK) at codons 72-76 of the chloroquine resistance transporter gene (pfcrt); three samples carried the resistant CVIET allele; one carried both the resistant and wild type, and in two samples the allele could not be analysed. Conclusions The absence of mdr1 gene copy number variation detected in this study suggests lumefantrine resistance has yet to emerge in KwaZulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation.</p