Adverse events to first line anti-tuberculosis drugs in patients co-infected with HIV and tuberculosis

Background: The combination and use of multiple drugs in the treatment of tuberculosis (TB) predispose to adverse drug events and reactions. This study evaluated the incidence, frequency, and severity of adverse events to first line anti-tuberculosis (anti-TB) drugs in patients with TB and co-infections with Human Immunodeficiency Virus (HIV).Objectives: The objective of this study was to determine the effects of HIV status on the risk of developing adverse events to first line anti-TB therapy.Method: The study was carried out between 2006 and 2007 when TB therapy was administered without concomitant anti-retroviral therapy. Patients with TB presenting at the chest clinic of a tertiary hospital were sequentially enrolled. Those with TB alone were allocated to the first group while those with TB-HIV infection were allocated to a second group. A checklist of adverse events to the drugs was used to screen for adverse drug events and reactions during the period of anti-TB therapy. Adverse drug events were graded as serious and others (mild-moderate).Results: One hundred and three patients completed the study. Thirty one (30.1%) of the patients had TB-HIV co-infection. Majority (70.4%) of the events were detected during the first week of therapy, 92% of these events were mildmoderate. Eight (25.5%) of those with TB-HIV co-infection had serious adverse events. All the serious events occurred in the TB-HIV group. Independent factors for occurrence of ADEs include HIV status, increasing age, and female gender.Conclusions: The rate of adverse drug events among patients on first line antituberculosis treatment was higher in HIV co-infected patients.Keywords: Adverse drug events; Tuberculosis; Anti-TB therapy; HIV co-infection, Nigeri

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Comparative study of efficacy of artesunate plus cotrimoxazole and artesunate plus chloroquine in the treatment of malaria in Nigerian children: a preliminary report

Background & objectives: The study was undertaken to evaluate the efficacy of cotrimoxazole plusartesunate and to compare the efficacy of this combination with that of artesunate plus chloroquinein the treatment of acute uncomplicated falciparum malaria in children.Methods: Children aged between 0.5 and 12 yr with clinical and parasitological evidence ofPlasmodium falciparum malaria were randomized to receive either artesunate plus cotrimoxazoleor artesunate plus chloroquine. They were followed-up with clinical and parasitological assessmentfor a period of 14 days.Results: In all, 57 out of 81 (31 in the artesunate plus cotrimoxazole group and 26 in artesunateplus chloroquine group) completed the study as per protocol and were evaluated. Pre-treatmentclinical and parasitological parameters were similar in the two treatment groups. The time to clearfever and other symptoms were similar in the two groups 1.0 + 0 vs 1.14 + 0.38 (p > 0.05).Parasite clearance times were also similar; 1.65 + 0.49 days vs 1.58 + 0.67 days respectively forartesunate plus cotrimoxazole and artesunate plus chloroquine (p > 0.05). The cure rates on Day14 were 100% for both artesunate plus cotrimoxazole and artesunate plus chloroquine groups.Both drug combinations were well-tolerated in the small population of children.Conclusion: These results indicate that artesunate plus cotrimoxazole has similar efficacy toartesunate plus chloroquine in the treatment of acute uncomplicated P. falciparum malaria inchildren resident in an endemic area of south-west Nigeria

Predictors of asymptomatic malaria in pregnancy

Summary: A number of studies have described malaria parasitaemia in pregnancy as mostly an asymptomatic condition, however information about predictors of asymptomatic malaria is largely lacking. We investigated the prevalence of symptoms and potential predictors of asymptomatic malaria in pregnant women attending Ante-Natal Clinic (ANC) of two public maternity hospitals in Ibadan, Southwest-Nigeria. Demographic data, history of previous and present pregnancy were obtained from the subjects and blood smears were examined for malaria diagnosis by light microscopy. Seventy – seven parasitaemic pregnant women attending antenatal clinic were evaluated for presence or absence of symptoms that may be associated with malaria. Thirty-seven women (48%) were asymptomatic whereas 40 (52%) presented with symptoms such as weakness, headache and general body ache and fever. Parasite density was significantly higher in symptomatic patients (P = 0.042), while asymptomatic patients had low level parasitaemia but significantly higher gametocyte carriage (P = 0.035). In conclusion, parasitaemic pregnant women resident in hyper- or holo-endemic malaria region are likely to be symptomatic with increasing density of the parasitaemia

Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: Double-blind randomised controlled trial

Background: Increasing resistance to sulfadoxine-pyrimethamine is leading to a decline in its effectiveness. We aimed to assess the safety profile of chlorproguanil-dapsone (CD), and to compare the safety and efficacy of this drug with that of sulfadoxine-pyrimethamine (SP) as treatment for uncomplicated falciparum malaria. Methods: We undertook a double-blind, randomised trial in 1850 consecutively recruited children with uncomplicated falciparum malaria, pooling data from five African countries. Analyses were based on all randomised patients with available data. Findings: CD was significantly more efficacious than SP (odds ratio 3·1 [95% CI 2·0-4·8]); 1313 patients (96%) given CD and 306 (89%) given SP achieved acceptable clinical and parasitological response by day 14. Adverse events were reported in 46% and 50% of patients randomised to CD and SP, respectively (treatment difference -4·4%, [95% CI -10·1 to 1·3]). Haemoglobin in the CD group was significantly lower than in the SP group at day 7, a difference of -4 g/L (95% CI -6 to -2). Mean day 14 haemoglobin (measured only for the small number of patients whose day 7 data caused concern) was 94 g/L (92-96) and 97 g/L (92-102) after CD and SP, respectively. Glucose-6-phosphate dehydrogenase deficient patients on CD had greater odds than those on SP of having a fall of 20 g/dL or more in haemoglobin when baseline temperature was high. Methaemoglobinaemia was seen in the CD group (n=320, mean 0·4% [95% CI 0·4-0·4]) before treatment, 4·2% (95% CI 3·8-4·6) (n=301) at day 3, and 0·6% (0·6-0·7) (n=300) at day 7). Interpretation: CD had greater efficacy than SP in Africa and was well tolerated. Haematological adverse effects were more common with CD than with SP and were reversible. CD is a useful alternative where SP is failing due to resistance